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Scientific Program

The Scientific Program at Vaccines-2014 will feature cutting-edge developments from scientists at every career stage, including world leaders in vaccines, immunology, allergy and all the relevant areas presenting their research in Keynote forum, plenary lectures and scientific sessions, young researcher presentations and poster presentations.

Note: 5-8 best posters will be awarded by the organizing committee
Website:
http://www.omicsgroup.com/vaccines-vaccination-conference-2014/
Submit Your Abstract Online at
http://www.omicsgroup.com/vaccines-vaccination-conference-2014//abstract.php
or e-mail to
vaccines2014@omicsonline.net
vaccines2014@omicsgroup.co
vaccines2014@omicsgroup.biz

Day 1 : Sep-24-2014
Keynote Forum

Alexander von Gabain

European Institute of Innovation and Technology

Keynote: How to foster innovation to meet the global gap of novel vaccines: Learnings from the European Institute of Innovation and Technology, EIT
Biography:
Alexander von Gabain obtained his Ph.D. in Genetics at the University of Heidelberg and held a post-doctorate position at the Stanford University. In the 1980s and 1990s, he was Professor at the University of Umeå and at the Karolinska Institute in Stockholm, Sweden, as well as an advisor to pharmaceutical and biotech companies. From 1992 to 1998, he was Chair of Microbiology of the University of Vienna at the Campus Vienna Biocenter, Austria and has helped to build the public private partnership of the Vienna Biocenter/IMP. In 1998, he cofounded Intercell AG and led the company as CEO until it was successfully floated on the Vienna Stock Exchange in 2005. From 2005 to 2009, he was Member of the Executive Management Board and CSO of the Company. Since then, he has been serving the Company as strategic advisor and chair of the Scientific Advisory Board.
Abstract:
Infectious diseases remain one of the greatest global challenges for both the developed and the less developed parts of the world. Vaccines are the most promising hope to control infectious diseases worldwide. The encouraging progress made in relevant scientific fields, but also in the arena of novel manufacturing technologies has enabled vaccine innovation, but still the number of novel vaccines coming to the customers is rather limited. Many believe that top class research and education per se lead to innovation. However, when taking a closer look at, how research, education and business create innovative chains of added value, it is clear that entrepreneurship plays a crucial role within the “knowledge triangle”. To overcome this dilemma, but also the fragmented innovation landscape in Europe, the EIT (European Institute of Innovation and Technology), was set up by the European Union in 2008. The EIT is devoted to create favorable ecosystems for entrepreneurship-driven innovation by joining the three sides of the knowledge triangle of research, higher education and business. At the heart of the EIT are the innovation factories, the so-called KICs. The EIT is providing seed money to the KICs that in turn are led and run by CEOs, on the basis of respective business plans. Each KIC works within five or six co-location centers spread across Europe and they enable people from universities, research centers, large and small businesses, and other relevant partners to work together face-to-face in integrated teams. This ensures that excellence driven innovation factories are real focal points of integration where innovation is facilitated. The first three KICs have been successfully implemented. Together they form 16 co-location centers across Europe and are addressing the following topics: climate change mitigation, sustainable energy and future information and communication society. The EIT will invest into a second wave of KICs which also will target health care challenges. I will discuss how the vaccine arena may be able to learn from the current experience to improve the build up of innovative ecosystems that meet the global challenges.






Keynote Forum

Maurizio Chiriva-Internati

Assistant Professor
Texas Tech Unviersity
USA

Keynote:
Biography:
Maurizio Chiriva Internati completed his doctorates of immunology at the University of Nottingham, United Kingdom and morphological sciences at the University of Milan, Italy. He completed his postdoctoral research on tumor immunology and cancer vaccine studies from the University of Arkansas for Medical Sciences. Currently, he is the director of Basic and Translational Research at the division on Hematology& Oncology at the Texas Tech University Health Sciences Center, School of Medicine, and is a senior editor for the journal, International Reviews of Immunology. He has published more than 100 papers in peer reviewed journals and serves as on the editorial board of several reputed cancer journals.
Abstract:






Keynote Forum

Nikolai Petrovsky

Director of Endocrinology
Flinders Medical Centre Research Director, Vaxine Pty Ltd.,
Editor in Chief
Journal of Vaccines and Vaccination

Keynote: Vaccine Adjuvants; the good, the bad and the ugly
Biography:
director of endocrinology at flinders medical centre with a conjoint position as professor of medicine at flinders university, nikolai petrovsky is also vice-president and secretary-general of the international immunomics society. active in diabetes, endocrinology and vaccine research, he is the founder of vaxine, a company funded by the us national institutes of health to develop novel vaccine technologies. in 2009 vaxine won the amp innovation award at the telstra business awards and australia's coolest company award from australian anthill magazine. nikolai petrovsky has developed vaccines against influenza, hepatitis b, sting allergy, malaria, japanese encephalitis, rabies and hiv, has authored over 90 papers and chapters and is a regular invited speaker at international vaccine conferences.
Abstract:
Hghly purified antigens suffer from poor immunogenicity. Current paradigms to address this problem focus onuse ofpotent innate immune activators as adjuvants, thereby mimicking natural infection. Unfortunately using this approachadjuvant immunogenicity and reactogenicity are largely inseparable.This talk will address the question of whether pro-inflammatory danger signals are really needed to make modern vaccines effective. Using examples of vaccines against influenza, West Nile virus, Japanese encephalitis virus and other important biodefense pathogens, data will be provided to show that bigger is not always better when it comes to vaccine adjuvants. Novel polysaccharide adjuvants such as delta inulin (Advax™) with more subtle immune effects surprisingly provide the best long-term immune memory responses and vaccine protection in the absence of generation of danger signals.






Keynote Forum

Michael G. Hanna

Chairman and Chief Executive Officer
Vaccinogen, Inc.
USA

Keynote: The practical influence of tumor genomic heterogeneity on active specific immunotherapy
Biography:
Dr. Hanna is a co-founder of Vaccinogen, Inc., the discoverer and developer of OncoVAX, Vaccinogen’s lead project, and a pioneer in the field of cancer vaccines. He also developed and obtained FDA approval for TICE BCG for treatment of carcinoma in situ ("CIS") bladder cancer which remains the standard of care for prophylaxis of recurrence of superficial bladder cancer and therapy of CIS.
Dr. Hanna has not only proven his capabilities as discoverer and developer of clinically beneficial biotherapeutics, but also has raised over $300 million for the final clinical development of OncoVAX. As the director of the National Cancer Institutes, Frederick Cancer Research Center, between 1975 – 1983, he created a center of research excellence and managed over 2,000 technologists consisting of hundreds of MDs and PhDs. A special committee of the National Cancer Advisory Board selected him for the above responsibilities.
He previously served as Chairman (Emeritus) and Chief Scientific Officer of Intracel Resources, an integrated biopharmaceutical company that developed cancer vaccines and immunotherapeutic and diagnostic products for both cancers and infectious diseases. Dr. Hanna also served as President and Chief Executive Officer of PerImmune, Inc. before it and Intracel Corp. merged in 1998. From 1985 to 1994, he was the Chief Operating Officer of Organon Teknika Biotechnology Research Institute and Senior Vice President of Organon Teknika Corporation, a subsidiary of Akzo Nobel, N.V., The Netherlands. Prior to that, he was Director of the National Cancer Institute, Frederick Cancer Research Center.
Dr. Hanna received a doctoral degree in experimental pathology and immunology from the University of Tennessee. He has over 225 publications to his credit, has 10 patents in immunotherapy and has been the recipient of numerous honors.
Abstract:
At the cellular level it is clear that cancer is a genetic disease arising as a clone that expands and grows in an unregulated manner. While it has always been presumed that neoplasia is a consequence of somatic cell mutations, only in the last few years has the magnitude and diversity of these mutations been elucidated by modern DNA sequencing technology. Immunotherapy is the premier biological approach to targeted therapy. Targeted therapies require targets. In this case the targets are tumor specific or associated antigens, the proteins expressed from these somatic cell mutations. While the immunotherapeutic approach to eliminating cancer was launched with the assumption that cancer cells were homogeneous, the recent genomic understanding of tumor cells indicates that there is both inter- and intra-tumoral heterogeneity. You cannot treat a heterogeneous disease with a hemogeneous treatment. This presentation will discuss the consequences of this new knowledge of tumor cell biology to the immunotherapeutic approach to treating cancer.






Keynote Forum

Ray Spier

Former President
International Society for Vaccines
UK

Keynote: Vaccines protective against diseases caused by antibiotic-resistant bacteria: A pressing challenge to Vaccinologists
Biography:
Having been educated at Christ Church, Oxford and University College, London in Biochemistry (First Class Honours), Chemical Microbiology and Biochemical Engineering he then spent 7 years as a Senior Process Engineer in industry. The last 3 years in America were spent with Merck Sharpe and Dohme where he was introduced to animal cell biotechnology and the production of viruses for use in veterinary and human vaccines. On returning to the UK he worked for 10 years at the Animal Virus Research Institute, Pirbright, scaling-up bioreactors for virus vaccine production processes and maximizing the biological productivity of the BHK cell lines for Foot-and-Mouth Disease virus generation. He then moved to the University of Surrey as Professor and was Head of Microbiology (7 years) and was then (1997) appointed to the first chair in the UK in ‘Science and Engineering Ethics’. His publication record includes over 200 research papers and reviews along with over 20 edited books and an encyclopedia on animal and plant cell culture technology. In 2002 his book ‘Ethics Tools and the Engineer’ was published by CRC Press. He is currently the Vaccine Series Editor in Chief, and Editor in Chief of Vaccine Research Quarterly, Procedia in Vaccinology, Trials in Vaccinology and ‘Science and Engineering Ethics’. Having founded the European Society for Animal Cell Technology in 1975 and the International Society for Vaccines in 1996 (President: 2007-11), he was elected to be President of the European Association for Higher Education in Biotechnology in 2000.
Abstract:
Since the publication of a WHO report on the threat to public health of antibiotic resistant bacteria (April, 2014) newspaper editorials and articles have been redolent with echoes of this imminent threat. These, as well as reports on this topic by the WHO and the CDC in the USA, have singularly failed to recognise that vaccines constitute the most cost- effective defence against this emergent situation.
The question is: why?
Some 90%+ of the money for R&D in the healthcare sector is spent on seeking therapeutic solutions to the alleviation of existing pain and disease. So there is an inbuilt bias to seek to adapt existing approaches to pathogenic bacteria based on the use of antibiotics as these have been close to miraculous. The question then becomes – how do we move from where we are to a new paradigm for antibiotic discovery and use? The stock answer to the emergence of antibiotic resistant bacteria is to blame the overuse of antibiotics so it becomes necessary to limit and regulate the way in which antibiotics are deployed. Another response is to discover more, and more effective, antibiotics. Others have considered the dropped concept of using Bacteriophages while yet seeking solutions in the molecular biology of the bacterial invasion process and the methods the bacteria use to become antibiotic resistant. There are even appeals for a change to the regulatory environment and to take special measures to encourageindustrial efforts to be reinvigorated. There is an alternative way to proceed. This would require a major investment in the R&D that leads to new and more effective vaccines that can protect individuals for much of their lifetime against pathogenic bacteria. Several new, dedicated, publicly funded and state-of–the-art Institutes have to be founded, built and staffed with the brightest and the best vaccinologists. And these Institutes should be guaranteed financial support for over 20 years in the first instance. My presentation will examine, the reasons for, and the method of implementation, of this proposal in more detail.






Keynote Forum

Charung Muangchana

Director
National Vaccine Institute
Thailand

Keynote:
Biography:
Charung Muangchana is a graduate of Bloomberg School of Public Health, Johns Hopkins University (JHU), Baltimore, USA (2007), for International Health (Disease Prevention and Control; Vaccine Science and Policy as well as Economic Evaluation on Health) for his PhD, and of Siriraj Hospital, Mahidol University, Thailand (1990) for his MD. He is also a field epidemiologist by training from the Ministry of Public Health (Field Epidemiology Training Program: FETP). He got many publications on international and domestic peer review journals on variety of health issues, including vaccine and immunization. He has been a director of the National Vaccine Institute (NVI) Thailand, since 2007. The NVI is a new institute at national level to coordinate national vaccine policy and strategy. The NVI aims to promote vaccine research and development as well as policy development on immunization in the country, which Thailand has high capacity on vaccine development and production. Before joining the NVI he worked as a medical practitioner and directors of community hospitals in Southern Thailand.
Abstract:






Vaccine adjuvants
Session Introduction

Alan R Shaw

Vedantra Pharmaceuticals
USA

Title: Inter-Bilayer Cross-linked Multi-Lamellar Vesicles (ICMVs) for efficient co-delivery of antigen and adjuvant payloads
Biography:
Alan R. Shaw, PhD, is Chairman and Chief Scientific Officer at VaxInnate Corporation where he is responsible for scientific and medical conduct of the company’s efforts to develop new vaccines incorporating pathogen associated molecular patterns. He joined VaxInnate in 2005 following a 15year career at Merck Research Laboratories where he was responsible for R&D leading to the licensure of Varivax®, ProQuad®, Zostavax®, RotaTeq® and Gardasil®.
Prior to joining Merck, Dr. Shaw was a Senior Program Executive at Biogen S.A in Geneva, Switzerland where he led projects on hepatitis B vaccines, malaria vaccines, cytokines and their inhibitors, and cell trafficking. Dr. Shaw was the Chairman of the International Federation of Pharmaceutical Manufacturers’ Association Biologicals Committee and has extensive experience in national and international vaccine development and policy matters.
Dr. Shaw received his Ph.D. in Molecular Biology and Biochemistry from the Medical College of Ohio, and was a post-doctoral fellow at the International Institute for Cellular Pathology in Brussels and at the Rockefeller University in New York. Dr. Shaw’s expertise is in the areas of virology, molecular biology, immunology and protein chemistry. He has served as an adjunct faculty member at Temple University in Philadelphia. He is currently a member of the NIH Board of Scientific Counselors.
Abstract:
Vaccine development generally involves a lot of work on the antigen aspect, some effort on formulation, and the addition of an adjuvant in some form or another. These components are often elaborated separately and delivered as a mixture, sometimes in an emulsion or in a liposome, with the hope that some fraction of the material administered gets to the right place. Recent work on materials engineering at MIT has brought together novel assemblies of lipid nano particles loaded with antigen and adjuvant, “hardened” by chemical cross-links to create a system that co-delivers its payload to lymph nodes. We call these particles ICMVs (Inter-bilayer Cross-Linked Multi-Lamellar Vesicles. By sequestering the adjuvant and antigen in a particle, systemic exposure is limited. This should result in an improved safety and tolerability profile. In mice, the optimal dose of antigen is on the order of a microgram. Adjuvants, engineered to fit into the nano particle, allow the use of very low doses as well. The result is a potent, long lasting humoral response accompanied by a robust antigen specific CD8+ T-cell response. ICMVs can be delivered by injection, but they may delivered by inhalation as well. Intratracheal delivery to the lungs results in a strong CD8+ response on mucosal surfaces with no apparent pathology. The application of ICMV mediated malaria vaccines will be discussed.






Siwicki Andrzej Krzysztof

University in Olsztyn
Poland

Title: Influence of natural and synthetic immunomodulators on the effectiveness of vaccines in fish
Biography:
Professor Andrzej K. Siwicki DVM, PhD, DSc is a head of Department Microbiology and Clinical Immunology on the University in Olsztyn and head of Department Pathology and Immunology in the National Inland Fisheries Institute in Olsztyn, Poland.
He is author or co-author of over 600 publications: about 400 original papers, 12 books and about 200 articles and scientific communications. His fields of interest: comparative clinical and experimental immunology, modulation of defence mechanisms and protection against infectious diseases by natural and synthetic products, develop a new generation of vaccines for animals, restoration of immunity after suppression induced by xenobiotics.
Abstract:
The protection of aquatic animals against diseases by immunization has been an important concept for many years. However, some vaccines when actually applied in aquaculture are not as effective as they should be. Natural and synthetic immunomodulators activate nonspecific defence mechanisms, cell-mediated immunity and specific immune responses in fish. Immunomodulators can be administered before, with, or after vaccines to amplify the specific immune response and protection against diseases in generating elevations of humoral antibody levels and the number of antibody-secreting cells (ASC). Special applications of natural and synthetic immunomodulators include assisting spray, injection and orally to increase the topical uptake of vaccines. In the present study, the influence of two natural (HMB, Leiber-BetaS) and two synthetic (methisoprinol, levamisole) immunomodulators on the cell-mediated and humoral-mediated immune response after immunization of rainbow trout with Yersinia ruckeri and Aeromonas salmonicida vaccines were determined. The immunomodulators were administered orally in pellets before, with, or after the vaccine applied by immersion. ELISPOT and flow cytometry assays were used for the quantification of cell-mediated and humoral-mediated immune response. Also the challenge test was used for study the protection against bacterial pathogens The percent of mortality after experimental infection were determined. The results showed that natural and synthetic immunomodulators increased the cellular and humoral immune response and protection against diseases, but results is determined by time of application before and after immunization.






Magdalena Tary-Lehmann

Chief Scientific Officer
Cellular Technology Limited
USA

Title: Adjuvant-guidance of T cell responses
Biography:
Dr. M. Tary-Lehmann is an Adjunct Associate Professor of Case Western Reserve University (CASE) Department of Pathology, Co-Founding Scientist and Chief Scientific Officer for Cellular Technology Limited (CTL). She has published more than 75 papers in peer-reviewed journals. She provides guidance and oversight for technical operations in the GLP laboratory, ensuring the ongoing scientific excellence of CTL. Over the past decade, she has worked with clients and regulatory agencies to develop and validate reference samples and controls for use in regulated immune monitoring assays.
Abstract:
Adjuvants are important enhancers of the immune response. The choice of adjuvant is especially crucial in the context of subunit vaccine approaches. In the past, adjuvants have been used with little knowledge of the mechanism by which they exert their effects. Studies on the role of adjuvants on CD4+ T cell responses have shown that different types of adjuvants can polarize the cytokine response while inducing the same proliferative capacity, specificity and avidity of CD4+ T cells. Such responses were shown to be independent of the antigen used and genetic background of the host. Would this also be the case for CD8+ T cells? What is the contribution or importance of providing CD4+ T cell help or toll-like receptor (TLR) ligation in the generation of these CD8+ T cell responses? Studies have shown that CD8+ T cells are guided differently than CD4+ T cells. In addition, it was found that the use of different adjuvants can induce the generation of different CTL populations: cells which kill but do not produce IFN-gamma, cells which do not kill but produce IFN-gamma, and cells which both kill and produce IFN-gamma. By understanding the extent to which one can guide the T cell responses through the use of adjuvants and appropriate CD4+ T cell help or TLR agonists, one can improve both vaccine efficacy and safety. These have broad implications not only for vaccine development, but also in the fields of autoimmunity, transplantation, and tumor biology.






Venky Ramakrishna

Celldex Therapeutics
USA

Title: Antibody targeting of human T cell CD27 identifies genes and pathways related to inflammation
Biography:
Dr. Venky Ramakrishna earned his Ph.D. in Immunology at The Weizmann Institute of Science, Rehovot, Israel with postdoctoral years in Italy’s Mario Negri Pharmacological Research Inst. in Chieti and the National Cancer Institute, Milano. He also holds an engineering degree from India’s prestigious Indian Institute of Technology in Kharagpur (WB) and lectin research at the Indian Institute of Science Bangalore. He formerly held R&D positions at Argonex Pharmaceuticals and Upstate Biotechnology (Charlottesville, VA) and Bristol Myers Squibb (formerly Medarex, Bloomsbury, NJ). He is currently Associate Director of R&D Immunology at Celldex Therapeutics (Hampton, NJ, USA) with several technology and research patents in US and Europe and well published in peer reviewed journals. His current interests include applying integrative biology and OMICS in translational medicine.
Abstract:
Monoclonal antibodies are increasingly being used as effective therapeutic tools to agonize or antagonize molecules involved in immune responses against cancer and autoimmunity. Celldex has recently characterized a fully human mAb to CD27 (CDX-1127), a TNFR superfamily member, currently undergoing evaluation in the clinic. Here we present the human in vitro characterization of T cell responses to an anti-CD27 agonistic mAb and show that it effectively provides co-stimulatory signals in a TCR-dependent manner. These events when further investigated in silico using global transcriptional profiling and network analysis revealed several up and down regulated genes that patterned as “early” and “late” events to uncover cytokines and pathways related to inflammation and representing potential biomarkers relevant for clinical application of our CD27 agonist mAb.






Brian K. Meyer

Merck & Co
USA

Title: Evaluation of ZOSTAVAX® via the intradermal route using the MicronJet™
Biography:
Brian K. Meyer is a Principal Scientist in Bioprocess Research and Development, Merck Research Laboratories. He completed his Ph.D. at The Pennsylvania State University. He has held various positions at Merck, both in the research and manufacturing divisions.
Abstract:
Here we report the results of intradermal vaccination studies that were performed with an attenuated virus (varicella; ZOSTAVAX®). Intradermal vaccination using the MicronJet™ by Nanopass Technologies was compared to the current route of administration (subcutaneous). It was demonstrated with ZOSTAVAX® that doses of 1/3rd and 1/10th the full dose elicited both antibody and T-cell responses that were equivalent to a full dose delivered subcutaneously. A full dose of ZOSTAVAX® administered intradermally resulted in a higher overall antibody titer when compared to the subcutaneous route.






Harry Kleanthous

Sanofi-Pasteur, Inc.,
USA

Title: Universal influenza vaccines: Prevention of infection against matched and mismatched strains
Biography:
Dr. Kleanthous has over 20 years industry experience in the research & development of recombinant live attenuated and subunit-based vaccines against viral and bacterial pathogens.
He joined sanofi pasteur as US Head of Discovery Research in 2008 with responsibility for evaluating and developing novel viral vaccine platforms and delivering novel targets to the Development pipeline. Previously, Dr. Kleanthous was Vice President of Research at Acambis Inc. (formerly OraVax) with responsibility for developing a new exploratory portfolio. His research interests are in the field of replication-defective viral vaccine platforms, targeting Influenza, Flaviviruses and Herpes viruses, as well as their use for foreign antigen delivery.
Prior to joining industry, Dr. Kleanthous was a scientific investigator at academic teaching hospitals and the Health Protection Agency (Colindale) in the UK, where he developed his expertise in the area of infectious diseases and molecular epidemiology. He obtained his Ph.D. in the field of Molecular Microbiology from the University of London.
Abstract:
Annual vaccination against seasonal Influenza A and B virus subtypes with well-matched inactivated virus (INV) vaccines are highly effective against upper respiratory tract (URT)Influenza infection and induced disease. Protection against infection is thought to be mediated principally by neutralizing antibodies targeting the receptor binding site (RBS) ofthe hemagglutinin globular head (HA1). Immune pressure on HA1 results in antigenic drift, necessitating worldwide surveillance with subsequent WHO recommendations on strain selection for manufacture of forthcoming seasonal influenza vaccines.
The development of Universal Influenza Vaccines (UIV) that could protect against matched as well as drifted or mismatched strains wouldprovide significant improvement over standard of care (SOC). Additionally, a target product profile that also offers long-lasting immunity wouldbe a substantial advantageof current annual vaccination practices, potentially enabling year-round manufacture. UIV that induce both breadth and durability across multiple influenza seasons would be paradigm shifting for the Influenza field and offer significant health care benefits.
As part of our universal influenza vaccine program, and using the H1 subtype as our proof of concept (POC), we have built both consensus-based, computationally optimized broadly reactive antigens (COBRAs), as well as designs displaying dominant epitope patterns, through Structural Mapping of Antigenic Repertoires (SMARt). These prototype designshave been demonstrated to fold properly, have the ability to bind conformation-specific mAbs(HA1 & HA2) as well asagglutinate red blood cells. Prototype H1N1 HA proteins were presented on virus-like particles (VLPs), tested in-vivo, and determined toelicit broadly cross-neutralizing functional antibody responses, protect against viral challenge, and preventtransmission in pre-clinical mouse and ferret models. This is the first report describing the induction of universal, broadly-reactive, protective immunity against H1N1 isolates using a consensus-based HA strategy focusing on the globular head.






Eric Gowans

The University of Adelaide
Basil Hetzel Institute
South Australia

Title: DNA vaccines which encode natural adjuvants are more effective than canonical DNA vaccines
Biography:
Eric Gowans is a Senior Research Fellow in the University of Adelaide. He has an interest in developing novel vaccine strategies for HIV and HCV and has published around 130 papers in reputed journals.
Abstract:
Although DNA vaccines are attractive, suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and the development of an effective immune response to the encoded antigens, has inhibited their potential. Consequently, we included the genes for membrane bound and secreted versions of HSP 70, which act as natural adjuvants, in DNA vaccines encoding the HIV protein, gag. Furthermore, as the non-cytolytic nature of DNA vaccination is likely to be a factor contributing to its inefficiency, a second vaccine encoding HIV gag and a cytolytic protein (perforin-PRF) that induces necrosis in vaccine-targeted cells after intradermal delivery was synthesized. This results in the expression and extracellular localization of damage associated molecular patterns, effective adjuvants that bind to pathogen recognition receptors in antigen presenting cells. Both vaccines generated greater cell mediated immunity resulting in significant increased protection against challenge with EcoHIV, a chimeric HIV that infects mice, compared with the canonical DNA vaccine. We also encoded PRF in a DNA vaccine encoding the HCV NS3 protein and vaccinated mice and pigs with this vaccine. The PRF-encoding vaccine generated statistically significant higher cell mediated immunity in mice and in pigs, as determined by ELIspot, after intradermal vaccination. To ensure effective, reproducible delivery the vaccine was delivered to the pig dermis by a microneedle device. As DNA vaccines fail to induce immunity to the vector, an effective DNA vaccine may be used in a homologous multi-dose regimen or as a DNA prime in a heterologous regimen.






Jean-Pierre Y. Scheerlinck

The University of Melbourne
Australia

Title: Immune memory resilience, a new way of evaluating adjuvants
Biography:
A/Prof Jean-Pierre Scheerlinck has obtained PhD from the Free University of Brussels (VUB, Belgium) and postdoctoral studies at the ILRI (Nairobi, Kenya), and WEHI (Melbourne, Australia). He than joined CSIRO (Australia) as a project leader and later moved to The University of Melbourne, where he currently holds the position of Director, Centre for Animal Biotechnology (CAB). The CAB is a Research Centre dedicated to developing and using animal models for biotechnological and biomedical exploration. He has published more than 70 papers and serving is an editorial board member of 4 peer-reviewed journals.
Abstract:
Adjuvants are traditionally assessed for their ability to enhance or modulate immune responses to a vaccine antigen, as measured by their capacity to induce strong primary immune responses, both cellular and humoral. More recently, the faculty of adjuvants to induce immune memory responses that are long-lived and can effectively be boosted has also been assessed. Here we propose a novel way of evaluating adjuvants, based on their ability to induce immune memory responses that are resilient to manipulation by pathogens. In most cases vaccines rely on the induction of immune memory responses, which are subsequently recalled during the early stages of infection. For many pathogens the recall of immune memory responses represent a real challenge to their survival resulting in significant evolutionary pressures on pathogens. As a result some pathogens have developed immuno-modulatory properties in an attempt to circumvent immune destruction. These mechanisms include manipulation of the recall response away from protective immunity. Hence there is a need to assess and optimize adjuvants for their ability to induce resilient immune memory responses, able to withstand such manipulation. Using a combination of adjuvants and model antigens we are developing ways of measuring immune memory resilience and propose that the induction of resilient immune responses should be a major consideration in designing novel vaccines.






Satoshi Uematsu

The University of Tokyo
Japan

Title: CD103+CD8α- LPDCs in small intestine are suitable targets for oral vaccines
Biography:
Dr. Satoshi Uematsu graduated from Osaka City University School of Medicine in 1997 and received his Ph.D. degree in Medicine from Osaka University in 1997. He is the professor of International Research and Development Center for Mucosal Vaccine, Institute for Medical Science, The University of Tokyo. Dr. Uematsu has authored or co-authored more than 150 scientific publications, reviews and book chapters.
Abstract:
CD103+ dendritic cells (DCs) are the major conventional DC population in the intestinal lamina propria (LP). Our previous report showed that low density cells in the LP could be classified into four subsets based on the difference in CD11c/CD11b expression patterns: CD11chiCD11blo DCs, CD11chiCD11bhi DCs, CD11cintCD11bint macrophages, and CD11cintCD11bhi eosinophils. We found that small intestine CD103+ DCs of the LP (LPDCs) could be divided into a small subset of CD8α+ cells and a larger subset of CD8α- cells. Flow cytometry analysis revealed that CD103+CD8α+ and CD103+CD8α- LPDCs were equivalent to CD11chiCD11blo and CD11chiCD11bhi subsets, respectively. CD103+CD8α+ LPDCs expressed TLR3, TLR7, and TLR9 and produced IL-6 and IL-12p40, but not TNF-α, IL-10, or IL-23, following TLR ligand stimulation. CD103+CD8α+ LPDCs induced antigen(Ag)-specific IgG in serum, Ag-specific Th1 response, and weak CTL activity in vivo. In contrast, CD103+CD8α- LPDCs, major populations of Ag-presenting cells (APCs) in small intestine specifically express the gene encoding retinoic acid-converting enzyme Raldh2 and are involved in T cell-independent IgA synthesis or Foxp3(+) regulatory T cell induction. Furthermore, they express TLR5 and TLR9 and induced Ag-specific IgG in serum, Ag-specific IgA in stool, Ag-specific Th1 abd Th17 responses, and strong CTL activity in vivo. Collectively, CD103+CD8α- LPDCs are suitable targets for oral vaccines from both quantitative and qualitative viewpoints.






Chih-Hsiang Leng

National Health Research Institutes
Taiwan

Title: Establishment of lipid-based immunogens for the development of novel subunit vaccines
Biography:
Chih-Hsiang Leng has completed his Ph.D from National Defense Medical Center, Taiwan and postdoctoral studies from Division of biotechnology and pharmaceutical research, National Health Research Institutes (NHRI). He is an associate investigator in National Institute of Infectious Diseases and Vaccinology, NHRI and is now working for the development of novel and effective recombinant subunit-based vaccines. He collaborated with his colleagues to develop novel polymer-based adjuvant for enhancing the potency of subunit vaccines and to establish a novel lipoprotein expression system to produce high potent lipo-immunogens for the development of novel subunit vaccines.
Abstract:
We have established a platform technology for high-yield production of recombinant lipoproteins. The lipid moiety of the produced lipoproteins is identical to that of bacterial lipoproteins, which are recognized as danger signals by the immune system. Thus, both innate and adaptive immune responses can be induced by lipoproteins. Ag473 (a lipoprotein from N. meningitidis) can be produced in high yields using E. coli strain C43 (DE3). After testing a non-lipoprotein (E3, from dengue virus) fused with different lipid signal peptides, we identified that a fusion sequence, D1, to express a recombinant lipoprotein, rlipo-D1E3, at high level. Multiple-stage fragmentation and immunological analysis demonstrated that the structure of recombinant lipoprotein was different from that of synthetic tri-acylated lipopeptide and it elicited different immune responses from synthetic lipopeptide by inducing different levels of biological cytokines and chemokines. The rlipo-D1E3 was found to elicit stronger virus neutralizing antibody responses than those from rE3 alone or rE3 formulated with alum adjuvant. Moreover, an inactive human papillomavirus (HPV) E7 (E7m) biologically linked to a bacterial lipid moiety (rlipo-E7m) induced the maturation of mouse bone marrow-derived dendritic cells through toll-like receptor 2, skewed the immune responses toward the Th1 responses and induced E7-specific CTL responses. We further validated that the rlipo-E7m was able to induce anti-tumor immunity against HPV associated tumors in a mouse model. The therapeutic efficacy of E7m was dramatically increased in its lipidated form. These results have successfully demonstrated the merit of lipo-immunogens for the development of novel subunit vaccines.






Pele Choi-Sing Chong

National Health Research Institutes
Taiwan

Title: Highly immunogenic C-terminal binding domain of clostridium difficile toxin a stimulates dendritic cell maturation
Biography:
Dr. Chong obtained his BSc and PhD from the department of Biochemistry in the University of Alberta, Edmonton, Canada. He was trained as a protein chemist and specialized in peptide synthesis for protein structure and function studies. Dr. Chong had spent 15 years at Connaught Laboratory Limited (now called Sanofi Pasteur) in human vaccine research and development. During his tenure there, Dr. Chong had developed two human vaccines, ProHibit against H. influenzae type b (Hib) and the component pertussis vaccine. In June/2003, Dr. Chong was recruited and joined NHRI to develop and establish the Vaccine Research and Development Center (VRDC). To facilitate and implement the Taiwanese Government Vaccine R&D, Self-Manufacturing and Supply strategic plans, VRDC starts from 1 person (Dr. Chong) and now has >140 staff operating the fully integrated Biotech-like organization structure. Dr. Chong has authored over 150 original research articles and has over 80 patents filed and/or granted.
Abstract:
Clostridium difficile (Cd) is implicated as opportunistically nosocomial infection in hospitalized patients due to disrupt the antagonistic balance in the intestinal micro-flora by prior antibiotic therapies. The major pathogenicity of CDI is correlated with clostridial toxins, toxin A and toxin B, secreted into the host gastrointestinal environment to disrupt barriers of epithelial cell in small intestine. Non-toxic domain on C-terminal regions of toxin A (tcdA) and toxin B (tcdB), responsible for cell binding and pathogenesis, are emerging targets for Cd vaccine development. In this study, we designed and expressed a recombinant C-terminal receptor binding domain of toxins rRBD). rRBD has been characterized and found to have cell binding and hemagglutination activity in vitro and rapidly internalized into cytosol and then be degraded quickly. Mouse immunogenicity studies indicated that rRBD can specifically elicit strong IgG antibody without any adjuvant at 10-30 ug dose in the BALB/c mice. Moreover, protection of rRBD immunization at 30 ug achieved 70% survival rate after lethal challenge of C. difficile toxin A. Indeed, this C-terminal binding domain is found to be capable of stimulating different immune cells to enhance immune responses. In addition, the results supported rRBD could directly upregulate surface markers of DC maturation and trigger cytokines secretion of IL6, IL12, and TNF-alpha. Thus, the activity of triggering DC maturation becomes one route which contributes to highly immunogenic property and could be a potent Cd vaccine component.






Hyo-Ihl Chang

Korea University
Korea

Title: The Cronobacter sakazakii ESP2949-1 phage induces dendritic cell maturation via activation of nuclear factor-κB and IL-12p40 in murine bone marrow
Biography:
Hyo-Ihl Chang has completed his PhD in 1987 from North Carolina State University. He has been professor of College of Life Sciences and Biotechnology, Korea University since 1988. He was a dean of College of Life Sciences and Biotechnology, Korea University. He has published more than 80 papers in reputed journals. Now he is a president of the Korean Society for Microbiology and Biotechnology.
Abstract:
Bacteriophages can be operated as highly immunogenic antigens, which could interact with dendritic cells as antigen presenting cells. The bacteriophage ESP2949-1 is a lytic phage of Cronobacter sakazakii which has been isolated from sewage samples. Unlike other phages that were researched as therapeutic agents for many diseases, the ESP2949-1 phage has never been clearly examined for therapeutic purpose. To evaluate its therapeutic effect, the production of the proinflammatory cytokines TNF-α, IL-6, IL-1α, and IL-1β, the expression of the dendritic cell maturation markers CD86 and CD40, and the underlying of NF-κB signaling pathways in murine bone marrow-derived dendritic cells (BM-DCs) in response to ESP2949-1 phage infection were studied. The bacteriophage ESP2949-1 affected the expression of the cell surface molecules and proinflammatory cytokines that are related with the DC maturation processes. Treatment with ESP2949-1 phage also induced the NF-κB-IL12p40 signaling pathways. Our chromatin immunoprecipitation assay(ChIP) showed that p65 could bind the IL12-p40 promoter via translocation to the nucleus which indicates the activation of NF-κB signaling. Furthermore, the ESP2949-1 phage induced the promoter activity of IL-12p40. Our ChIP assay also revealed that p65 was enriched at the IL12-p40 promoter as a direct target of chromatin. The present study demonstrates that the ESP2949-1 phage potently induces DC maturation via immune-enhancement processes.






Didier Betbeder

University of Luille2
France

Title: Nasal administration of antigens using maltodextrin nanoparticles: a mechanistic study
Biography:
Betbeder Didier is professor of physiology at the University of Artois and Lille, France. He has 20 years experience in mucosal vaccine using colloids, ranging from basic research to clinical studies. Working with WHO he obtained his PhD in 1988 on drug targeting to treat sleeping sickness, before spending 2 years as a post-doctoral fellow at the University of Warwick (England). He joined Biovector Therapeutics (France) as Research director to develop nasal flu vaccine using nanoparticles as adjuvant. He has been a Professor at the University of Artois and Lille since 2001 and has over 60 international publications and 21 patents to his name. He is board member SFNano since 2013 and was president of the French control release society (GTRV) from 2004-08.
Abstract:
Nanoparticles can be used to deliver antigens to immune cells, therefore increasing their immunogenicity. A better knowledge of their mechanisms of interaction with cells and the biological fluids is necessary to fully understand their potential as delivery systems of antigens. Most of nanotechnologies-antigens complex to formulate proteins implies surfactant, organic solvents, temperature conditions all these parameters are generally considered to be deleterious from proteins and is a limitation for further medical applications. To overcome these inconveniences, we developed a new concept based on porous nanoparticles to obtain protein loading in water without requiring any organic solvent or surfactant. These nanoparticles made from starch hydrolysate (maltodextrin) can be used alone or associated with lipids. Proteins loaded are efficiently rotected from proteolysis and antigens are highly delivered within cells and when administered intra-nasally or sub-linguallly this delivery vehicle was capable of eliciting humoral, cellular and mucosal immunity without the use of adjuvant. This lecture will give an overview of the mechanisms implied using nanoparticles to deliver antigens to the immune cells using the nasal route of administration.






Lakshmi Krishnan

National Research Council-Human Health Therapeutics
Canada

Title: Novel Lipid based Adjuvants and Delivery Systems for Induction of CD8 T cell immunity
Biography:
Lakshmi Krishnan completed her Ph.D. from the National Institute of Immunology in India and postdoctoral studies from University of Alberta, Canada. She is the Team Leader for Immunomodulation and flow cytometry facility at NRC. She is also the Adjuvant Technologies Lead of the NRC-vaccine program management team and an Adjunct Professor at the University of Ottawa. She has published >50 articles in peer reviewed journals and is an inventor on several patents. She collaborates with vaccine industry leaders and has received funding from the Ontario Institute for Cancer Research, Canadian Institutes of Health Research and National Institutes of Health (USA).
Abstract:
Novel adjuvants hold promise for developing modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however their translation into routine clinical use is lagging.
At the National Research Council (NRC) of Canada, we are leading efforts in the development of novel lipid adjuvants and delivery systems. Archaeosomes, prepared from isoprenoid lipids extracted from archaea, are one such adjuvant in development. Archaeosomes have both stand-alone immuno-modulator and carrier properties for vaccine antigens. Our innovation includes use of semi-synthetic archaeosomes, wherein an archaeal core lipid serves as a lipid precursor for synthesis of a series of glyco-archaeols and phospho-archaeols. In this way archaeal synthetic lipid mimetics not limited to those found naturally in Archaea, were screened to optimize the carrier/adjuvant effect desired. Modified formulations or archaeal lipids also evoke a strong mucosal immunity. Furthermore, we have developed novel recombinant bacterial and adenoviral vectors for expression of vaccine antigens. Our development processes focus on ensuring cost-effective bioprocessing, scale-up and regulatory considerations alongside efficacy. To bridge innovation gaps and unmet needs for hastening the development of adjuvants and vaccines from bench to clinical testing we have recently identified an opportunity for creation of a Canadian Adjuvant Development Network. Furthermore, we are developing bioanalytics for correlates of vaccine protection. This presentation will detail our key adjuvant technologies and vaccine biomarker research.






Maria Helena Bueno da Costa

Scientific Consultant
France

Title: Stabilized liposomes carrying bee venom new formulation is the breakthrough of pain and anaphylaxis and death in mice under Venom immunotherapy
Biography:

Abstract:
Stings from bees, wasps, and ants produce a variety of clinical and histological manifestations. Anaphylaxis following an insect sting is the most serious complication. For individuals with a specific allergy to Hymenoptera venom, the venom immunotherapy (VIT) may be a relatively effective treatment. However, treatment failures occur and VIT may cause frequent systemic allergic side effects, mainly in honeybee allergic persons. The VIT is expensive and time consuming. New strategies to improve safety and efficacy of this treatment are therefore of general interest. We developed, step by step, a systematic approach to study the basic and biotechnological problems related to the design of a safe formulation of bee venom (BV) within liposomes to be used in VIT. It is known that mellitin (Mel) is the major toxic peptide in the European honey bee venom (50 % of the wet weight) and that it has a powerful hemolytic activity and is responsible for local pain. Phospholipase A2, another BV component, also interacts and disrupts membranes. The inhibition of PLA2 and Mel activities through histidine alkylation, and or tryptophan oxidation (with pbb, para-bromo-phenacyl bromide and/or NBS- N-bromosuccinimide respectively) was envisaged to allow their encapsulations within stabilized liposomes. We strongly believed that this formulation (modified venom within stabilized liposomes) should be non toxic but immunogenic. The characterization of the total bee venom conformation, during and after chemical modification, as well as after interaction with liposomes, was undertaken using ultraviolet, circular dichroism and fluorescence spectroscopies. The PLA2 and Mel biological activities were measured indirectly by changes in liposomal turbidity measured at 400nm, rhodamine leak-out and haemolysis. The S-A-BV (Succinilated and alkylated BV) interacted with liposomal membranes without causing aggregation, leak-out or fusion (ILS, 2007). Here, we detailed (by confocal microscopy) the interaction between native or Mel or BV chemically modified with GUVs (Giant Unilamellar vesicles). These results were compared to freeze-fracture electron microscopy images, which corroborated the previously observed S-A-BV (succinilated and alkilated BV) or Mel/liposome interactions. A stable formulation composed of S-A-BV encapsulated within liposomes composed of SPC:Cho:pbb, 26: 7: 1 was employed. Large unilamellar vesicles of 202.5 nm with a negative surface charge (-24.29 mV) encapsulated 95 % of S-A-BV. Mice injected with this formulation did not show venom toxicity signals. Two reasons could be ascribed to this effect: a. either, the Mel molecule or total BV lost their hemolytic activity through chemical modifications or b. the liposomal encapsulation avoided direct contact between animals with Mel or BV. Once more we observed that the liposomal vehicle has adjuvant properties. This formulation prevented anaphylaxis and death in mice during a challenge with native BV. The IgE was absent in these mice. This safe formulation can, now, be used in humans.






Jude E Uzonna

University of Manitoba
Canada

Title: Identification of highly immunogenic and protective Leishmania major antigen that elicits strong T cell recall responses in recovered human patients
Biography:
Dr. Uzonna obtained DVM and Ph.D. in Immunology from the University of Saskatchewan, Canada. After a postdoctoral fellowship at the University of Pennsylvania, USA, he was recruited to the Department of Immunology, University of Manitoba in 2004. His research program focuses on understanding cellular and molecular mechanisms that regulate the induction, maintenance and loss of protective immunity to protozoan parasites, with a view to exploiting the information gained from these studies for the development of effective vaccines and vaccination strategies against these infections. Dr. Uzonna is currently an Associate Professor of Immunology and the Leader of Parasite Vaccines Development Research Group.
Abstract:
Despite a plethora of publication on immunology of leishmaniasis, there is still no clinically effective vaccine against the disease. We used reverse immunology and proteomics approaches to identify naturally processed L. major peptides presented by MHC II molecules on infected mouse dendritic cells. One of the peptides derived from highly conserved glycosomal phosphoenolpyruvate carboxykinase (PEPCK), induced strong proliferation and IFN- production by CD4+ T cells from infected mice. PEPCK is expressed in glycosomes of L. major promastigotes and amastigotes and also induced proliferation, IFN- and granzyme production in PBMCs from infected human patients that healed cutaneous leishmaniasis. Vaccination with PEPCK peptide, DNA or recombinant protein induced strong protective immunity against L. major challenge in both the resistant and susceptible mice. Importantly, we generated PEPCK peptide-MHC II tetramer and reliably demonstrate the activation, expansion, effector activity, contraction and stable maintenance of PEPCK-specific CD4+ T cells in L. major-infected mice. Thus, reverse immunology and proteomics-based antigenic peptide identification approach is a potentially rewarding strategy to find new vaccine candidates for infectious pathogens






SandybayevNurlan

Deputy of General Director
Research Institute for Biological Safety Problems
Republic of Kazakhstan

Title: Live vaccine for equine influenza on the base of cold-adapted recombinant strain A/HK/Otar/6:2/2010
Biography:
Dr.SandybayvNurlan received a PhD degree in microbiology in 2007. He is the Deputy General Director of the Research Institute for Biological SafetyProblems at the Ministry Education and Science of the Republic of Kazakhstan and the Principal Investigator for molecular biology of viruses at the Laboratory of Molecular Biology and Genetic Engineering.
Dr.Sandybayevhas authored and co-authored more than 172 scientific articles and abstracts, 7 books, and holds 34 author’s rights for his work on PCR methods, viral and bacterial strains, DNA and RNA sequencing and vaccine development.
Abstract:
A new strategy of vaccination for equine influenza (EI) is developing in last years in the western countries, especially in North America. Live vaccines from attenuated strain influenza virus are produced for more natural stimulation of immune systems. Immune responsecaused by natural infection,as opposed to immunity stimulated by inactivated vaccines, is more adequate and longer because of stimulation cellular and humoralimmune response.
The method of classical genetic is used for construction of recombinant strain for a candidate in vaccines. As donor HA and NA are used strain A/equine/Otar/764/07(H3N8) equine influenza virus actual for Kazakhstan and so high yield and cold-adapted strain A/Kong Hong/168/162/35 (H3N2) (phenotype ts+ and ca+). The basic scheme of receiving of reassortants is provides the following selective passages of parental viruses at presence of sera. The recombinant strain A/HK/Otar/6:2/2010 having HA and NA genes from the virulent strain and the internal genes from vaccine strain is result. Correspondence of genomic composition of reassortant is confirmed by PCR and sequencing. Absence of pathogenicity and toxicity on embryonated chicken eggs and the laboratory models are shown. The stability of reassortant genome is shown on more than 20 passages in the embryonated chicken eggs.
Live cold-adapted vaccine for prophylactic of equine influenza is produced on the base of strain A/HK/Otar/6:2/2010 (phenotype ts+ and ca+). Vaccine safety for foals, pregnant mares and adult horses is shown. The rates of humoral and cellular immunity of horse immunized by vaccine are studied. Expressed protective of vaccine challengeafter of horses by the virulent strain A/horse/Otar/764/07(H3N8) are shown. Animals of the vaccine challenge areprotected 100 % from disease. On duration of immunity, the twofold vaccination is protected from disease within 12 months.






Megha Kadam Bedekar

Central Institute of Fisheries Education
India

Title: Role of Interferon gamma as immune adjuvant in Labeorohita
Biography:
Megha Kadam Bedekar completed Bachelor of Veterinary Science degree in 1999, and secured gold medal for best thesis research work for Master's degree. She completed PhD in Animal Biotechnology from Indian Veterinary Research Institute and joined Animal Biotechnology Centre, Jawaharlal Nehru Veterinary University, Jabalpur India, as Assistant Professor in 2005. In 2011 she got selected as Senior Scientist in Central Institute of Fisheris Education, Mumbai. Her areas of specialization are animal biotechnology, immunology, and microbiology. She developed PCR based diagnosis system and database of Infectious bronchitis virus strains of India and novel vaccine construct against Mycobacterium avium paratuberculosis. Currently, she is working on development of bicistronic vaccines against important bacterial diseases of aquatic animals.
Abstract:
Economics of fish farming industry is severely affected with problems due to a variety of infectious agents that includes both bacterial and viral pathogens. Immune system of fishes is less developed compared to higher vertebrates. Therefore responsibility of the fisheries scientists is more towards development of better vaccination strategy that can activate both specific and non-specific immune response.Interferon gamma (IFNγ) is the key cytokine which activate inflammatory and Th1 subset of immune response against bacterial and viral diseases.Addressing to the important role of IFNγwe have cloned and studied the effect of rIFNγ on immune system of labeorohita, which is one of the most economically important fresh water carp in India. We have cloned and expressed 551 bpIFNγ open reading frame of Labeorohita in SSN-1 cell line using eukaryotic expression vector system. The SSN-I cell linewas transfected and at 24h and 48h post-transfection, 18.7kDAIFNγ protein was expressed in these cells, which was confirmed by Western blot with anti-his antibodies. This IFNγ construct was also transfected in peripheral blood lymphocytes (PBMCs) and checked for expression of four genes IFNγ, iNOS, MX and IL-1β by real-time PCR. Significantly high expression of all four genes was observed in IFNγ-treated group compared to mock transfected group at 24h and 48h time-points in terms of fold increase (p<0.05). IFNγ and iNOS showed the peak expression at 24h and remained at the same level until 48h. However, MX and IL-β1 were found to be highly up-regulated at 48h compared to 24h. The results showed the conserved function of IFNγand up-regulation of these genes indicated the role of IFNγin anti- bacterial, anti-viral and inflammatory responses. Our study highlights the candidature of IFNγ as immunoadjuvant along with vaccine against fish pathogens.






Seyed Davar Siadat

Pasteur Institute of Iran
Iran

Title: Outer membrane vesicle of bacteria: Friend or Foe?
Biography:
Seyed Davar Siadat is Associate Professor of Medical Microbiology at Pasteur Institute of Iran. He has an extensive research portfolio in bacterial vaccines; especially in “Outer Membrane Vesicle” based vaccines, Subunit vaccines, Conjugate vaccines, etc. He has published more than 70 papers in scientific journals (National & International) and serving as editorial board member/reviewer of several scientific Journals from the field of Medical Microbiology and Infectious Diseases. He has mentored and supervised many students for their thesis or summer scholarship program. He has guided 20 Ph.Ds and More than 30 MSc students.
Abstract:
Outer membrane vesicles (OMVs) are released from the many Gram negative bacteria such as Neisseria meningitidis, Vibrio chlora , Bordetella pertusis, Acintobacter bumani , Brucella spp ,etc. The OMV components consist of a phospholipid bilayer, outer membrane proteins, periplasmic constituents and lipopolysaccharide. This macromolecule has multifunctional activity as described by many researchers previously. The befit of the bacterium; It has been proposed that OMV involved in several activities exhibited by bacteria such as pathogenesis and useful interaction in colonization and biofilm production as well as transformation of drug resistance in chronic and acute infections. Likewise, OMVs are mechanisms that bacteria can secrete many virulence factors such as toxins, enzymes and periplasmic & membrane compartments. The benefit of the host; Among many scientific reporters, OMV of Neisseria spp have well known that could be applied as carriers of polysaccharide in conjugated vaccine, adjuvants activity in combined vaccines, drugs delivery in biological systems and also employed as vaccine subunit against N. meningitidis serogroup B. According these properties of OMV, the adjuvants capacity of OMVs have been well mentioned as well as other aspects of functional activity of OMV. Thus OMV are likely employed as a benefit macromolecule with microbial origin in vaccine research and development studies. This lecture describes the general principles of OMV behavior, summarizes what is currently known and discuses the multifunctional activities of OMV.






Arfa Moshiri

Shahid Beheshti University of Medical Sciences
Iran

Title: Adjuvant properties of outer-membrane-vesicle in Hepatitis B surface based vaccine
Biography:

Abstract:
Objective: The outer membrane vesicle of Neisseria meningitidis serogroup B (OMV) is among the more studied components with microbial origin, which could be applied as an adjuvant. In the present study, OMV of N. meningitidis serogroup B was applied as an adjuvant co-administrated with the HBs Ag to evaluate the efficiency of this immunization strategy for the promotion of efficient humoral/cellular responses against Hepatitis B virus.
Methods: OMVs were prepared as previously described (Siadat et al., 2005). In brief, N. meningitidis serogroup B strain (CSBPI, G-245) was grown under controlled submerge cultural condition in a fermentor containing modified Frantz medium. The outer membrane vesicles (OMVs) were extracted in Tris-HCl buffer, containing EDTA and deoxycholate. Purification of the OMVs was done by sequential centrifugation at 20,000 followed by ultracentrifugation at 125,000. Purified recombinant Hepatitis B surface antigen (HBsAg) was prepared from the production and research complex of Pasteur Institute of Iran (Karaj ,Iran). Four animal groups were immunized by intranasal inoculation with HBs, HBs+OMV mixture, HBs+complete/incomplete Freund's adjuvant (C/IFA) and OMV. Two booster immunizations carried out three and six weeks after the first immunization. Indirect enzyme-linked immunosorbent assay (ELISA) was applied to assess total and subtype antibody responses against HBsAg.
Results & Conclusion: Analysis of anti-HBsAg responses elicited in immunized BALB/c mice following different immunization regimens indicated OMV+HBsAg as an immunopotent combination which significantly induced anti-HBsAg IgG with IgG2a dominancy. In accordance to previous study, evaluation of humoral responses following the immunization with HBsAg, HBsAg+C/IFA and HBsAg+OMV indicated the potency of HBsAg vaccine in all the administrated formulations to efficiently induce humoral responses against HBsAg. Although the highest level of antibodies was raised in HBsAg +C/IFA injected animals, however, the promoted response in HBsAg +OMV immunized group was comparable with HBsAg +C/IFA, indicating the capability of HBsAg +OMV immunogen for humoral response induction. All of these responses are TH1 oriented with IgG2a sub-type predominance. The highest IgG2a titer has been detected in the sera of mice immunized with HBsAg +C/IFA respectively followed by HBsAg +OMV and HBsAg. Although the most augmented anti-HBs humoral responses were detected in the sera of HBsAg +C/IFA-immunized mice, however, titer of total anti-HBs antibody and raised IgG2a was significantly increased by the application of OMV adjuvant and was comparable with the HBsAg +C/IFA regimen. Considering that OMV is a human-compatible adjuvant, this finding argues in support of probable application of OMV in HBsAg -based vaccine. According to our study, HBsAg combined with OMV seem to be a promising adjuvant in vaccine development against Hepatitis B virus.






Bjarne Bogen

K.G. Jebsen Centre for Research on Influenza Vaccines
University of Oslo and Oslo University Hospital
Norway

Title: DNA vaccine that target hemagglutinin to MHC II-molecules rapidly induces antibody-mediated protection against influenza
Biography:
Bjarne Bogen is professor of immunology at the University of Oslo, Norway. He is director of K.G. Jebsen Centre for Research on Influenza Vaccines. He has been member of the Basel Institute for Immunology (1985-86) and visiting professor at Stanford University School of Medicine (1996-97) and Harvard University (2004-05). One of his research interests is development of novel DNA vaccines (Vaccibodies) that target vaccine proteins to antigen presenting cells. Based on patent applications on Vaccibodies, a company (Vaccibody) has been established. Bogen is head of the scientific panel of the company.
Abstract:
New influenza A viruses with pandemic potential periodically emerge due to viral genomic reassortment. In the face of pandemic threaths, production of conventional egg-based vaccines is time consuming and of limited capacity. We have now developed a novel DNA vaccine where viral hemagglutinin (HA) is bivalently targeted to Major Histocompatibility Complex (MHC) class II molecules on antigen presenting cells (APCs). Following DNA vaccination, transfected cells secreted vaccine proteins that bound MHC II on APCs and initiated adaptive immune responses. A single DNA immunization induced within 8 days protective levels of strain-specific antibodies, and also cross-reactive T cells. During the Mexican flu pandemic, a targeted DNA vaccine (HA from A/California/07/2009) was generated within 3 weeks after the HA sequences were published online. These results suggest that MHC II-targeted DNA vaccines could play a role in situations of pandemic threats. The vaccine principle should be extendable to other infectious diseases.






Jagusztyn-Krynicka Elżbieta Katarzyna

University of Warsaw
Poland

Title: Mucosal vaccine delivery system based on lactic acid bacteria (LAB)
Biography:
E.K. Jagusztyn-Krynicka obtained her PhD in 1974 from University of Warsaw. She became full professor in 2004. She worked twice ( 1989 – 1981, a post-doctoral fellow and 1989 –1991, a senior research associate) within prof. R. Curtiss III group. She is a head of research group involved in education and research. The group carries out fundamental and applied work on two pathogenic bacteria – Campylobacter and Helicobacter. She is the director of the Institute of Microbiology. She has published more than 45 of original research papers published in English in peer-refereed international journals as well as numerous review articles.
Abstract:
The lactic acid bacteria (LAB), which constitute a very heterogeneous group of Gram-positive, non-sporulating, low-GC-content microorganisms and are ubiquitous in many nutrient rich environments, represent an attractive alternative for vaccinations employing attenuated bacterial pathogens. Apart from live LAB cells also nonliving TCA pretreated LAB cells (GEM particles - grampositive enhancer matrix) deprived of some surface components and intracellular content constitute safe and efficient vaccine delivery vectors for heterologous proteins. There are two strategies used to present heterologous antigens on the surface of LAB cells. The first approach makes use of the C-terminus of a cell–anchoring proteins, which contain LPXTG motif. This mechanism requires processing by a sortase for covalent anchoring of the protein to the cell wall peptidoglycan. The second approach based on PA (protein anchor) domain of some lactococcal proteins such as AcmA, the major autolysin of Lactococcus lactis required for cell separation and responsible for cell lysis during the stationary phase of growth. The PA comprises three LysM motifs consisting of about 45 amino acids separated by spacer sequences. After secretion AcmA is directed to the cell wall and its C-terminus determines its noncovalent binding to cell wall peptidoglycan. Campylobacter spp., mainly C. jejuni, are a leading cause of zoonotic enteric bacterial infections in most developed and developing nations worldwide. An attempt to generate LAB surface display system for C. jejuni antigens will be presented.






Onuigbo Ebele

University of Nigeria
Nigeria

Title: Evaluation of the efficacy, safety and immunity of chitosan-based oral fowl typhoid vaccine
Biography:

Abstract:
Salmonella enterica serovar Gallinarum (S. Gallinarum) is the causative agent of fowl typhoid (FT). S. Gallinarum (SG) resides in the gastrointestinal tract after oral contamination and results in 80 % mortality of susceptible birds. Fowl typhoid has been eradicated in developed countries by stringent biosecurity measures and vaccines but is still of considerable importance in many developing countries. The local live attenuated FT vaccine produced by National Veterinary Research Institute (NVRI), Jos, Nigeria is given subcutaneously which is cumbersome in the vaccination of large numbers of chickens. Oral delivery of the local FT vaccine has not yet been fully exploited. Oral FT vaccine would also be beneficial to rural farmers in developing countries like Nigeria who cannot access veterinarians easily. Therefore, a safe and efficient oral delivery system is needed. In this research, we are developing a thermostable oral fowl typhoid vaccine encapsulated in alginate-coated chitosan nanoparticles. Chitosan is a natural cationic polysaccharide that has the ability to enhance the immunogenicity of antigens. It is non-toxic, biodegradable and mucoadhesive. However, chitosan is hydrophilic and is easily soluble in acidic solutions, hence, the coating with an acid-resistant polymer such as anionic alginate sodium onto the surface of chitosan nanoparticles. Alginate-coated chitosan nanoparticles protects vaccines better from degradation in acidic solution (pH 1.5) than the chitosan nanoparticles alone. From various in-vitro stability studies done in the past, alginate-coated chitosan nanoparticles conferred thermostability on the associated antigen. Formulation, characterization and thermostability of the coated chitosan nanoparticles would be performed. Immunogenicity and safety studies of the formulated oral alginate-coated chitosan FT vaccine would be compared to the parenteral commercial FT vaccine.






RandaHamadeh

Ministry of Public Health
Lebanon

Title: Polio outbreak in the Middle East –Update
Biography:
Randa Hamadeh is the head of the Primary Health Care department, and the manager of Immunization and Essential Drugs Program at the Lebanese Ministry of Public Health. She contributed to creating a PHC network in Lebanon through which preventive programs and community health initiatives could be initiated, usually involving local municipalities and NGOs. Mrs. Hamadeh contributed to the introduction of the PHC facility accreditation program in Lebanon in 2008, and is the vice chair of the national accreditation committee. Mrs. Hamadeh has actively participated in the foundation of various NGOs. She is the author of many public health papers and booklets. She holds an MPH degree, and a Vaccinology Diploma and is currently a senior lecturer in the faculty of Health Sciences at the Antonine University in Lebanon.
Abstract:
A comprehensive outbreak response continues to roll out across the Middle East following confirmation of the polio outbreak in Syria. As of 20 March 2014, some cases have been reportedin the Syrian Arab Republic: The most recent case had onset of paralysis on 17 December 2013. Further evidence of regional spread was confirmed lately by notification of a WPV1 case from Iraq, the first polio case in the country since 2000. The case developed paralysis on 10 February 2014. Genetic sequencing indicates the virus is most closely related to virus detected in the Syrian Arab Republic. Prospects for rapidly controlling this event are positive, as Iraq has been part of a regional Middle East emergency outbreak response since confirmation of polio in the Syrian Arab Republic. However and in response, all countries of the WHO Eastern Mediterranean Region, in a joint resolution, declared polio eradication to be an emergency, calling for support in negotiating and establishing access to those children who are currently unreached with polio vaccination. WHO and UNICEF showed high commitment to working with all governments to help vaccinate all children including Syrian children no matter where they are: In Lebanon, and as the risks of polio grows across the Middle East, the Ministry of Health launched an urgent national immunization drive to stop the disease regaining a foothold in Lebanon after an absence of 13 years. In addition to that, efforts have been ongoing to strengthen subnational surveillance sensitivity to ascertain the full extent of transmission, and since October 2013, 24 supplementary immunization activities (SIAs) have been conducted across the region to reach more than 22 million children with multiple doses. Larger-scale outbreak response across the Syrian Arab Republic and neighboring countries will continue, to last for at least 6 to 8 coming months depending on the area and based on evolving epidemiology.






Veterinary vaccines
Session Introduction

Priyabrata Pattnaik

Director – Worldwide Vaccine Initiative
Merck Millipore
Singapore

Title: Quality and consistency of cell culture media with a highlight on FMDV
Biography:
Dr. Priyabrata Pattnaik is Director of Worldwide Vaccine Initiative of Merck Millipore. He is global technical/market lead for vaccine program supporting R&D and integrated solutions for vaccines and thought leader on vaccine technology. He was head of Biomanufacturing Sciences and Training Centre at Singapore and lead a group of process engineers providing consulting services, educational seminars and applications support on Merck Millipore's Process Solutions, products and technologies.
Dr. Pattnaik worked as a Scientist at International Centre for Genetic Engineering and Biotechnology (United Nations), New Delhi for Malaria Vaccine Initiative [MVI] developing malaria vaccines. Later moved to Defence R&D Organization, Ministry of Defence, Govt. of India to lead the biodefence vaccine program. He was principal investigator for several vaccine projects and awarded by Indian govt with Brig. KM Rao award for his contribution on dengue vaccine development. He also supervised graduates and PhD students and lectured in several universities. He is the co-author of more than 80 publications in international journals and eight book chapters. He is also member of many scientific associations and in reviewer panel of several international journals.
Priyabrata Pattnaik graduated at the Utkal University of Orissa, received master degree in Microbiology from Orissa University of Agriculture and Technology, and awarded PhD in Microbiology from National Dairy Research Institute, India.
Abstract:
The GMP requirements for veterinary vaccine processes are very similar to GMP requirements for human vaccine manufacturing. All materials should be subjected to a risk assessment and testing when necessary, in particular, raw materials derived from humans and animals, which can be a primary source for the introduction of adventitious agents.
One of the challenges related to the production of FMDV is the ability to produce a highly potent vaccine at low cost, while improving process efficiency and maintaining regulatory compliant production environment. Complex cell culture media is used for propagation of BHK21 cells for FMDV production. The typical media is a GMEM base formulated with TPB and Lactalbumin. Most of the media contains also adult bovine serum (as high as 10%) but during virus incubation stage, the serum containing media is removed and the virus propagation happens in fresh serum free media. The use of more defined media composition without serum becomes a must, mainly due to the high variability of serum, the risk of introducing adventitious agent in the process, the fact that serum may contain antibodies against FMD and the associated cost of supply and serum treatment before it enters into the process. This presentation will describe how advancements in raw material procurement, characterization and processing has led to new high quality Cell Culture media standard that enables FMDV Vaccine manufacturers to resolve a long standing paradigm – the elimination of serum from their cell culture process.






Jean L. Patterson

Texas Biomedical Research Institute
USA

Title: Vaccine development at animal biosafety level four: Standards and challenges
Biography:
Dr. Patterson received her Ph.D. from the University of Notre Dame. She did postdoctoral studies at the Department of Biochemistry at the University of Wisconsin-Madison and the Department of Microbiology at the University of Geneva Medical School, Geneva, Switzerland. Before her appointment as Chair of Virology and Immunology at Texas Biomed she was on the faculty of Harvard Medical School. She has published over a 100 manuscripts in peer reviewed journals. She has served on numerous committees examining the use of high containment labs, such the NIH Blue Ribbon Panel for the Supplemental Risk Assessment for Boston University’s ABSL-4 laboratory.
Abstract:
The specific operation and safety procedures for the select agent Animal Biosafety Level Four (ABSL-4) at Texas Biomedical Research Institute in San Antonio, TX (Texas Biomed) has been operational at the BSL-4 level for 13 years and as an ABSL4 for 10 years. All precautions are taken to protect staff, the surrounding community and the environment from any hazardous biological materials. The guidelines originally come from Biosafety in Microbiological and Biomedical Laboratories issued by the Centers for Disease Control and Prevent (CDC) and the National Institutes of Health (NIH) 5th edition, NIH Guidelines for Research involving Recombinant and Synthetic Nucleic Acid Molecules, OSHA regulations and any other applicable federal, state and municipal regulations. All protocols and risk assessments are submitted and approved by the Biohazard and Safety Committee and Recombinant DNA Committee for work with all select agents in the ABSL-4. Recently some pathogens have been deemed Tier 1 meaning they are considered the most likely to cause a serious outbreak. New regulations for working with BSL-4 agents, that are Tier 1, require an institutional suitability assessment which determines an employee’s ability to abide by biosafety and biosecurity guidelines. This presentation will discuss how institutions maintain a high containment facility. How risk assessments are performed and how institutions monitor employees for their suitability to continue to work with select agents particularly Tier 1 agents.






Heather L. Wilson

International Vaccine Centre (VIDO-InterVac)
University of Saskatchewan
Canada

Title: Low dose antigen exposure in extreme early life promotes adaptive immune response in lambs and piglets
Biography:
Heather L Wilson completed her Ph.D. from the University of Saskatchewan, Canada and her postdoctoral studies from Vaccine & Infectious Disease Organization (VIDO). She is currently a Research Scientist at VIDO focusing of oral vaccination in neonates using pigs as an animal model. She has published more than 30 journal articles and reviews. Her projects are currently funded by Saskatchewan Agriculture Development Fund, Ontario Pork, and Alberta Livestock and Meat Agency.
Abstract:
Mucosal tolerance is defined as a state of antigen-specific non-responsiveness to oral antigens that prevents local and peripheral overreaction to oral antigens. In newborn lambs, the gut-wall is semi-permeable for up to 36 hours after birth allowing maternal antibodies from the colostrum to enter the suckling neonate’s circulation. We propose antigen introduced in extreme early life can readily access the gut-associated lymphoid tissues (GALT) and circumvent induction of mucosal tolerance. To test this hypothesis, newborn lambs were fed low doses of ovalbumin (OVA) starting immediately after birth for either a single day, for 3 consecutive days, or 9 consecutive days. At 4 weeks of age, lambs were immunized with OVA in Incomplete Freund’s Adjuvant (IFA) via intraperitoneal (i.p.) injection. Lambs gavaged with low dose OVA for 9 days developed significant serum anti-OVA IgG titres (prior to i.p. injection), but low IgA titres, and these titres were augmented after i.p. immunization (day 50). These lambs showed significant anti-OVA IgA titres in lung washes indicating induction of mucosal immunity. When splenocytes were re-stimulated with OVA ex vivo, the group of newborn lambs administered OVA for 3 days produced significantly higher IFN-γ expression relative to media-stimulated cells suggesting induction of antigen-specific, Th-1 biased cell-mediated immunity. Thus, perinatal antigen exposure primes local and distal mucosal antibody production as well as cell-mediated immunity in newborn lambs.
To establish if one dose prior to ‘gut-closure’ was sufficient to induce an immune response, piglets were drenched with OVA the day after birth and then boosted at 4 weeks of age with OVA with IFA via i.p. route. We observed a significant induction of OVA-specific serosal IgG and IgA antibody production, modest induction of IgG antibody production in the lungs, but low induction of cell-mediated immunity from restimulated lamina propria lymphocytes. Thus, while a single oral dose exposure of OVA was sufficient to prime the serosal immune response, it was not sufficient to induce robust mucosal or cell-mediated immunity. Thus, we observed that adaptive immunity can be induced in lambs and pigs to a soluble antigen (even in the absence of adjuvants) if oral exposure occurs very early in life.






Lijuan Yuan

Virginia Polytechnic Institute and State University
USA

Title: Study immune correlates of vaccine-induced protective immunity against rotavirus infection and diarrhea using B cell deficient neonatal gnotobiotic pigs
Biography:
Dr. Yuan completed her Ph.D. at The Ohio State University and post-doctoral training at NIAID, NIH. She is an Associate Professor at Virginia Tech. Dr. Yuan has published 67 peer-reviewed publications, including 48 research papers, 13 invited reviews and 7 book chapters. She serves as ad-hoc reviewer for Journal of Virology, Virology, Vaccine, and many other journals (33 different journals), serves on special review panels for NIH from 2009-2014 (5 study sections); for NSF in 2013 and 2014; and for Wellcome Trust and several other international funding agencies. She is the recipient of Pfizer Award for Research Excellence in 2011.
Abstract:
Determinates of protective immunity induced by human rotavirus vaccines have not been clearly identified. Our previous studies have demonstrated a significant correlation between virus-specific intestinal IgA antibody secreting cell responses and serum IgA titers and protective immunity against rotavirus shedding and diarrhea. In this study we used cloned gnotobiotic pigs with homozygous (-/-) disruption in the gene encoding immunoglobulin heavy chain (HCKO) to discriminate the function of effector T-cells from B-cells and antibodies in protective immunity conferred by an attenuated human rotavirus (AttHRV) vaccine. HCKO pigs are confirmed incapable of producing antibodies. Similar as in wild type (WT) pigs, 2 oral doses of AttHRV vaccine significantly reduced the duration and severity of diarrhea and fecal virus shedding upon virulent rotavirus challenge in HCKO pigs. Importantly, there were significantly higher frequencies of IFN-γ producing CD8+ T cells and NK cells in HCKO pigs compared to WT pigs at post-inoculation day 28 and post-challenge day 7. Consistent with the greater effector T-cell responses, the HCKO pigs had significantly lower frequencies of total Tregs and IL-10 producing Tregs compared to WT pigs. Increased virus-specific IFN-γ producing CD8+ T cells and NK cells in the HCKO pigs may have functioned in a compensatory manner to reduce diarrhea and virus shedding titer, but did not affect the onset and duration of virus shedding, suggesting that prevention of initial virus infection requires B-cell mediated immunity. Depletion of CD8+ T cells in HCKO pigs further discriminated the function of cytotoxic CD4+ T cells from CD8+ T cells.






Eric Cox

Ghent University
Belgium

Title: Targeting aminopeptidase N on enterocytes rapidly induces an IgA response in a pig model
Biography:
Eric Cox completed his PhD at the University of Ghent in 1991. He became assistant-professor at the Laboratory of Immunology in 1993, full professor in 1999 and director in 2008. Since 1993 he has performed research on intestinal immune responses in pigs using infections with enterotoxigenic E. coli (ETEC) as a model. This resulted in the discovery that pigs can be orally immunized with the purified fimbriae of F4+ETEC. He is promoter of the UGent valorisation consortium PROVAXS. He has published more than 200 papers in peer-reviewed journals and serving as associated-editor of Frontiers in Mucosal Immunity.
Abstract:
Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea in human and animal. In piglets, ETEC having F4 fimbriae (F4 + ETEC) induce severe diarrhea, dependent on the presence of receptors for F4 (F4R). We demonstrated that oral immunization with purified F4 fimbriae resulted in a serum and intestinal IgA response . The fimbriae become taken up by clathrin-mediated endocytosis. Porcine aminopeptidase N (pAPN) was identified as one of the receptors recognized by F4 fimbriae by comparative proteomic analysis of brush border proteins of F4R+ and F4R− pigs and by adherence / internalization experiments on pAPN-transfected cells. Binding of F4 fimbriae to pAPN depended on sialic acid containing carbohydrate moieties. Endocytosis via pAPN was not restricted to F4 fimbriae, but was also observed for anti-pAPN antibodies. Oral immunization with these antibodies iunduced a rapid immunoglobulin A and G response. In conclusion, we identified pAPN as an endocytotic receptor for F4 fimbriae and highlight the opportunity to target vaccine antigens to this epithelial receptor.






Silvia Pellicer

World Pathol
Spain

Title: Use of ORF-1 product Rep in prevention and diagnosis of Porcine circovirosis
Biography:

Abstract:
Economical loss produced by PMWS (Postweaning multisystemic wasting syndrome) is one of the most important issues that concern the pig industry. PMWS is considered a multifactorial disease in which development Porcine circovirus 2 (PCV2) is essential but not sufficient. Besides PMWS, PCV2 infection has been associated with some other pathological outcomes in pigs, collectively named porcine circovirus diseases (PCVD). PCV2 is a small non-enveloped virus belonging to Circoviridae family. Its genomic organization consists of two head to head arranged open reading frames (ORF1 and ORF2) separated by an origin of replication. ORF2 encodes the structural capside-forming protein Cap, the main immunogenic antigen of the virus. PCV2 infection is spread in farms all over the world. However, only a small percentage (4-30%) of infected animals develop PMWS. This fact has been related to the efficiency of host immune system humoral response. In order to fight against PCV2 infection spread in farms, it is essential to vaccinate the animals and to detect, as soon as possible, a PCV2 outbreak. Our preliminary results in overexpression in E. coli and purification of the protein encoded by ORF-1, Rep, are hereby showed. Use of Rep in vaccines against PCV2 would improve their efficacy and would allow to develop test to differenciate vacunated from infected pigs (DIVA).






Daniela Pencheva

Bul Bio - NCIPD Ltd
Bulgaria

Title: Properties of ghost bacterial cells obtained by hybrid material with silver nanoparticles (PVA / AgNps) as well as their opportunities for use in vaccine prophylactics
Biography:
Daniela Pencheva graduated on 25 years Masters Degree in the Biological Faculty of Sofia University "St. Kliment Ohridski ", Bulgaria. 33 years old she completed postgraduate Microbiology at the "Medical University", Sofia, Bulgaria. In 2012 defended PhD degree in “NCIPD”, Sofia, Bulgaria. She is head of laboratory in QC Department in “Bul Bio – NCIPD” Ltd. Sofia, Bulgaria. Until now has 9 published papers in reputed journals and 25 poster presentations and proceedings in Bulgarian and international congresses and conferences. She participate in a training process and is research consultant of students and young scientists with interest in microbiology and biomedicine.
Abstract:
PVA/AgNps is hybrid material with thermally reduced silver nanoparticles, stabilized in polyvinyl-alcohol. It is well characterized with experimental results from physico-chemical, microbiological and cytological tests. In vivo experiments in dermal cytotoxicity test and subcutaneous injections on white mouse showed PVA/AgNps as a non-toxic in the enclosed silver concentration. It was conducted an experiment to implement it as an inactivator of a bacterial strain E. coli O 104 for the preparation of antigen for immunization of rabbits. It has been used also for preservative of the obtained in consequence of immunization hyperimmune E. coli O104 rabbit antiserum. It has been successfully used in clinical trials as a treatment agent for cough and recurrent otitis in dogs. The activity of PVA / AgNps was tested to nearly 150 bacterial and fungal strains. The MBC of synthesized samples of the hybrid material are determined also for E. coli O 149, E. coli O 157 H7 and S. Typhimurium, which are established as common pathogens in farm animals with huge losses for animal farming. As a result of all the in vitro and in vivo tests, the hybrid material was characterized as a non-toxic product with a bactericidal and fungicidal action to control and clinical strains of bacteria and yeast in the established tests limits, with excellent prospects to be used as a preservative for diagnostic serums and as an inactivator for obtaining of ghost cells with capacity for application as whole cell killed vaccines, and theoretical perspectives in the preparation of recombinant vaccines.






Ríona Sayers

Animal & Grassland Research and Innovation Center
Ireland

Title: Imapct of three inactivated bovine viral diarrhoea (BVD) vaccines on bulk milk p80 (NS3) ELISA readings in commercial irish dairy herds
Biography:
Ríona Sayers holds a degree in Veterinary Medicine (MVB) and a Master’s degree (in prion biology) from University College Dublin, and a B.Sc. (Hons) in biochemistry from University College Cork. She has just completed a PhD with the university of Limerick titled “Biosecurity, Bovine Viral Diarrhoea Virus (BVDv), and Bovine Herpesvirus-1 (BoHV-1): Epidemiological investigations in Irish Dairy Herds”. She is a member of Animal Health Ireland’s BVD, IBR, and Johne’s disease expert technical working groups and has a growing publication record. She previously worked for commercial companies for 13 years in the area of veterinary diagnostics.
Abstract:
Vaccination is an integral component of Bovine Viral Diarrhoea virus (BVDv) control and eradication programmes. Surveillance programmes for detection of exposure to BVDv often incorporate bulk milk (BM) testing for the presence of anti-P80 (NS3) antibodies. Vaccination, however, can interfere with interpretation of results. The aim of this research was to complete a field-based study investigating interference from administration of three commercially available BVDv vaccines on p80 ELISA readings in a nationally representative group of commercial dairy farmers in the Republic of Ireland. A total of 305 commercial dairy herds, of which 256 were suitable for statistical analysis, were investigated using bulk milk ELISA (p80 and total antibody) analysis and spot testing of youngstock. Bulk milk samples were collected on four occasions over 2009 to allow investigation of seasonal trends. Herds were classified on the basis of bulk milk seropositivity, BVDv vaccination status, and whether evidence of recent BVDv circulation existed i.e. a positive spot test. Comparisons across varying herd classifications and vaccine types were completed using Wilcoxon rank-sum test and ROC analysis. Of the three vaccines investigated, only a single vaccine did not materially interfere with BVDv bulk milk antibody readings. Administration of this particular vaccine therefore has to potential to allow more accurate interpretation of bulk milk results in seropositive herds, relative to the other vaccines studied. Biologically significantseasonal differences in vaccinated herds were not detected. The results of this study are likely to prove useful in countries allowing vaccination during or post-BVDv eradication where bulk milk antibody surveillance strategies are required.






Chetan V. Jawale

College of Veterinary Medicine
Chonbuk National University
Republic of Korea

Title: Construction of Phix174 gene E mediated lysis system for generation of SalmonellaEnteritidis ghost, and its evaluation as a vaccine candidate for the immunogenicity and protective efficacy against avian salmonellosis
Biography:
Dr.ChetanJawale is basically a Veterinarian, currently pursuing Ph.D in Veterinary Medicine at college of Veterinary Medicine, Chonbuk National University, South Korea. He completed his B.V.Sc. and A. H. (2002-2007) from Bombay Veterinary College, Mumbai, India, and M.V.Sc in Animal biotechnology (2007-2009) from Anand Agricultural University, Anand, India. During 2009-2010 he worked as junior scientist at Xcelris Genomics Center, Ahmedabad, India. His research primarily focuses on the development of the recombinant and genetically inactivated vaccines against the Salmonella and E. coli infections in the domestic animals.
Abstract:
A new strategy to develop an effective vaccine is essential to control food-borne Salmonella entericaserovarEnteritidis infections. Bacterial ghosts (BGs), which are non-living, Gram-negative bacterial cell envelopes, are generated by expulsion of the cytoplasmic contents from bacterial cells through controlled expression using the modified cI857/λ PR/gene E expression system.During our initial studies, we have generated S.Enteritidis ghost using the antibiotic resistance gene containing pJHL99 lysis plasmid carrying the mutated lambda PR37-cI857 repressor and PhiX174 lysis gene E.Temperature induction of the lysis gene cassette at 42°C revealed quantitative killing of S.Enteritidis. In the development of genetically inactivated bacterial vaccines, plasmid retention often requires the antibiotic resistance gene markers, the presence of which can cause the potential biosafety hazards such as the horizontal spread of resistance genes.In order to overcome this issue, the new lysis plasmid was constructed by utilizing the approach of balanced-lethal systems based on auxotrophic gene Aspartate semialdehyde dehydrogenase (asd).The PhiX174 lysis gene E and λPR37-cI857 temperature-sensitive regulatory system was cloned in the asd gene positive plasmidand this novel approach allowed the production of antibiotic resistance marker free S.Enteritidis ghost. Although the generation of the S.Enteritidis was successful by using the above mentioned approach, but the unwanted leaky expression of lysis gene E occurred in the absence of induction temperature, and the bacterial host cell death during the normal growth condition at 28oC. To avoid leaky expression of the bacterial host-toxic PhiX174 lysis gene E from the λPR promoter, aconvergent promoter construct was made in which gene E was placed between a sense λPRpromoter and an anti-sense ParaBAD promoter. In the presence of L-arabinose, leaky transcription of lysis gene E at 28oC from the sense λPR promoter was repressed by an anti-sense RNA simultaneously expressed from the ParaBAD promoter. The stringent repression of lysis gene E in the absence of induction temperature resulted into higher concentration of bacteria in culture suspension, and consequently higher and stable production of a S.Enteritidis ghost. The S. Enteritidis ghost produced by above described approaches was characterized using scanning and transmission electron microscopy to visualize the transmembrane tunnel structure and loss of cytoplasmic materials, respectively.
The efficacy of the bacterial ghost as a vaccine candidate was evaluated in a chicken model. The chickens from all immunized groups showed significant increases in plasma IgG and intestinal secretory IgA levels. The lymphocyte proliferation response and CD3+ CD4+ and CD3+ CD8+ T cell subpopulations were also significantly increased in all immunized groups. The data indicate that both humoral and cell-mediated immune responses are robustly stimulated. Based on an examination of the protection efficacy measured by observations of gross lesions in the organs and bacterial recovery, the candidate vaccine can provide efficient protection against virulent challenge.






Zachariah E. Makondo

Tanzania Vaccine Institute
Tanzania

Title: Insights of vaccine production challenges in developing countries; current status in Tanzania
Biography:
Zachariah E. Makondo has completed his PhD from Sokoine University of Agriculture (SUA) and currently a senior Veterinarian and Public Health specialist at the Tanzania Veterinary Laboratory Agency (TVLA) / Tanzania Veterinary Institute (TVI) under the Ministry of Livestock and Fisheries Development of the United Republic of Tanzania. He is the TVLA head of Microbiology department and a Biorisk officer. He has undertaken over five contracted scientific research projects, and consultancy services in the public health, environmental issues, and socio economic studies. He has been an External Examiner/Referee and reviewer for numerous institutes and Universities, i.e. examinations moderator and academic staff referee/evaluator (e.g. candidates for professional positions).
Abstract:
Vaccine production in developing countries is a challenging subject that requires attention. Tanzania is one of the developing countries in sub-Saharan Africa that strife to overcome the dilemma. These shortfalls lead to vaccine production underperformance. Several issues were studied and analysed during development and production of veterinary vaccines in the Tanzania Vaccine Institute. Vaccine production, marketing and sales, Research on vaccines and scientific innovation / technology development were critical issues in this subject. I-2 Newcastle vaccine, Anthrax and Black quarter vaccines were developed and produced in 2012/3. The lesson learnt from the production, distribution and usage of these vaccines countrywide could justify continued efforts to produce other vaccines locally in a stringent manner. Studies underway include Brucella vaccine - S19 and Contagious Bovine Pleuropneumonia (CBPP) vaccine development that will finally lead to production in local setting. Vaccines are of critical importance for the control of infectious diseases and valuable to majority poor individual farmers in Tanzania. Limited financial resource, private sector inappropriate and poor technological development hinders the initiatives towards implementation of the ongoing vaccine development projects.






Inkar Castellanos

Viren SA de CV
Mexico

Title: Use of viral interference against avian influenza and establishment of protection levels in field outbreaks
Biography:
Inkar Castellanos has completed his veterinarian studies at the age of 23 years from Faculty of Veterinary Medicine U.N.A.M., later working in private industry, returning to study his M. S. at UNAM, by studying the expression of recombinant proteins in plant tissue. He is the Director of research and development of VIREN SA DE CV Company, a Mexican producer of vaccines and veterinary supplements. He has directed projects aimed to the study of influenza virus, The basis of his studies have been the expression of recombinant proteins and the development of products for the control of avian influenza. Two of these projects have been under a research grant support.
Abstract:
Use of viral interference against avian influenza and establishment of protection levels in field outbreaks in Mexico. Avian influenza currently is a critical problem present in poultry farming worldwide. Its prevalence in Mexico, despite vaccination, has highlighted the need for new approaches to control avian influenza and reduce the economic losses associated with its occurrence in susceptible birds. The different interactions between avian influenza viruses and cellular receptors have been described, along with the affinity of some viruses for certain types of species-specific receptors. This receptor–ligand specificity, combined with an understanding of viral interference processes and their relevance in different viral models, permits the assessment of new strategies for controlling avian influenza virus. The present study was designed to investigate the feasibility of using viral interference as a novel approach for avian influenza virus control, taking advantage of the high receptor–ligand specificity between avian influenza virus and animal cells. The results from field outbreak tests and cell culture analysis along with measurements of specific antibodies against avian influenza virus demonstrate that the mortality associated with avian influenza infection can be reduced by using a receptor blocker against avian influenza virus. This receptor blocker approach also has the potential to be used on an industrial scale for the efficient control of avian influenza virus. Others affinity molecules that block avian influenza virus - cell interaction has been proposed, but the difficulty of manufacturing on an industrial scale and the effectiveness of these molecules under field outbreak conditions have not been established.






Ana Paula Junqueira-Kipnis

Universidade Federal de Goiás
Brazil

Title: A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against Tuberculosis
Biography:
Ana Paula Junqueira-Kipnis has completed her Ph.D at the age of 30 years from Universidade de São Paulo and postdoctoral studies from Colorado State University, Fort Collins, CO and Albert Einstein College of Medicine, New York, NY. She is the head of Immunopathology Laboratories for infectious Diseases at Federal University of Goias, Brazil. She has received a prize for innovation in public health by Sanofis Laboratory in 2012 for design a new vaccine for TB. She has published more than 40 papers in reputed journals and serving as a reviewer board member of several reputed journals.
Abstract:
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used in TB prevention is the Mycobacterium bovis- BCG that presents a variable efficacy in protecting against pulmonary TB. Thus, the development of new vaccines with superior BCG protection efficacy has been the target of several studies. Here we constructed a new recombinant BCG vaccine expressing a fusion protein composed of immune epitopes from Ag85C, MPT51 and HspX (CMX) and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained up to 20 days post vaccination. rBCG-CMX is highly phagocytized by peritoneal macrophages and induces NO production. After mouse vaccination, this vaccine induced specific immune response to the fusion protein in cells from lungs and spleens. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific Th cells. The vaccine reduced almost half a log of the lung bacterial load when compared to BCG vaccinated animals. This study shows a new promising vaccine for tuberculosis posing a candidate for clinical trials.






Shoor Vir Singh

Central Institute for Research on Goats
India

Title: Therapeutic vaccination for the control of Johne’s disease using native strain of Mycobacterium avium subspecies paratuberculosis in animals: Can it be a model for the control of TB and leprosy in human beings and animal TB globally
Biography:
Dr. S.V.Singh, has completed his Ph.D at the age of 38 years from College of Veterinary Sciences in Mathura (UP), India. He has been awarded National Jawaharlal Nehru Award to ICAR for his doctoral work. He has been working as scientist (Veterinary Microbiologist) since 1984 in the Central Institute for Research on Goats, Makhdoom, Mathura, India and as Head of Animal Health Division since 2011 in the same institute. He has published more than 145 papers in reputed national and international journals and serving as editorial board member of reputed journals.
Abstract:
Mycobacterial infections plagued human and animal populations since existence of life on earth causing more miseries in the two species than all the bacterial pathogens of the two species combined together. Mycobacterium tuberculosis (M.tb.) and M. leprae are important pathogens of humans. Tuberculosis (TB) and M. avium subspecies paratuberculosis (MAP) are the two most prevalent infections of humans and animals, respectively. One third of world's human population is estimated to be infected with M. tb, though only one tenth of infected persons develop clinical TB. M. bovis and MAP are important pathogens of livestock and infect wide range of wild animal species worldwide. M. bovis and MAP bear a zoonotic potential (Cosivi et al., 1998; Singh et al., 2007). Since MAP is not in-activated during pasteurization also has public health significance. Despite investing huge resources on diagnosis, control and management, the pathogens load has increased in intensity and prevalence. In developing countries 40 to 80% of AIDS patients are at risk of developing TB or Johne’s disease (JD). Emergence of multi-drug resistant strains of M. tb., increased numbers of highly susceptible immuno-compromised individuals arising from AIDS pandemic. Extreme (XDR) or totally (TDR) drug resistant TB and leprosy raises possibility of epidemic of mostly drug-resistant TB and leprosy. It would jeopardize the progress made in recent years to control tuberculosis globally. Patients with XDR or TDR will need treatment same way as tuberculosis patients before antibiotic era.






Faisal Siddique

University of Agriculture
Pakistan

Title: Comparison and immunogenic evaluation of thermostable NDV I-2 and lassota vaccines against newcastle disease virus in Pakistan
Biography:

Abstract:
The current trial was conducted to assess the efficacy of thermostable vaccinal strain I-2 in field conditions of district Faisalabad, Punjab, Pakistan. For this purpose, five different poultry farms were randomly selected and day-old chicks were targeted and vaccinated through drinking water method. After administration of vaccine, three hundred and sixty blood samples were collected. The antibody titer was examined through indirect haemagglutination test (HI) and Enzyme linked immunosorbant assay (ELISA). Optimum average mean HI (Log2) and ELISA mean antibody titers was achieved at day 14 i.e. 7.324 and 6684, respectively, as compared with commercially available Lassota ND vaccine corresponding to 4.25 and 3850, respectively. Thermostable I-2 Newcastle disease strains were found to be more protective, safer and immunogenic and have produced significantly protective hummoral immune response in broilers against Newcastle disease, whereas in comparison to this, currently available Lassota ND vaccine produced poor antibody response. In conclusion, thermostable I-2 ND strain should be the preferable and clean choice for the farmers in developing countries like Pakistan in the future as intermittent electric supply due to the electric load shedding and high ambient temperatures are major hurdles in operating poultry industries.






Therapeutic vaccines for chronic infections
Session Introduction

Geert Vanden Bossche

REGA Institute, University Leuven
Founder and CSO of UNIVAC llc
Belgium

Title: Re-thinking Vaccinology
Biography:
Geert Vanden Bossche obtained his DVM at the Veterinary Faculty of Ghent and his PhD in Virology at the University of Hohenheim, Stuttgart. Following his postdoctoral training in virology, immunology and molecular biology at the Free University of Berlin and Hohenheim (Germany), where he subsequently held adjunct faculty appointments, he transitioned to the Vaccine Industry where he served various senior roles in both early and late vaccine development at GlaxoSmithKline Biologicals, Novartis Vaccines & Diagnostics and Solvay Biologicals. He then joined the Bill & Melinda Gates Foundation to serve as SPO in Vaccine Discovery for Global Health. He is founder of UNIVAC llc in the US and UNIVAC NV in Belgium and visiting scientist at the REGA Institute, University of Leuven (Belgium). Geert is board certified in virology and microbiology, the author of over 30 publications, and inventor on several patent applications. He has presented vaccine- and adjuvant-related topics at multiple international congresses.
Abstract:
To eliminate safety risks related to infectivity, inactivated pathogens and, more suitably, well-characterized pathogen-derived antigens (Ags) have increasingly been used as immunogens in ‘modern’ vaccines. The selection of these Ags is usually based on their capacity to naturally induce immune responses that ‘correlate’ with protection.. These Ags, however, are known to be antigenically variable (e.g., conformational Bc epitopes) and/ or subject to immunogenetic restriction (e.g., linear, cell-bound epitopes). In addition, the immunogenicity of ‘good’ vaccinal Ags is largely dependent on memory CD4+ T helper cells. However, activation of the latter upon natural infection or foreign Ag exposure of genetically predisposed subjects has been associated with immune pathology. Priming of CD4+ T helper cells by adjuvanted vaccines is, therefore, increasingly raising safety concerns. On the other hand, Ags that are highly conserved and of vital importance to the pathogen (hence, called ‘protective’) are either not included in contemporary vaccines or not effectively recognized by the host immune system since either deprived of cognate CD4+ T help or outcompeted by other pathogen-derived ‘decoy’ epitopes for binding to MHC molecules. Hence, we consider that new technologies enabling immune targeting of such protective epitopes by natural, universal (i.e., MHC-nonrestricted) immune helper cells is the new Holy Grail for modern vaccinology.






Jeffrey Ulmer

Novartis Vaccines & Diagnostics
USA

Title: Technologies for new and improved vaccines
Biography:
Dr. Jeffrey Ulmer received his B.Sc. with honors from the Department of Chemistry at the University of Regina in 1978 and was the recipient of the Merit Award of the Society of Chemical Industry of Canada. He received his Ph.D. in biochemistry from McGill University in 1985 and completed his postdoctoral training in the laboratory of Nobel laureate Dr. George Palade in the Department of Cell Biology at Yale University School of Medicine. At Merck Research Laboratories and Chiron Corporation he conducted seminal studies on DNA vaccines, and novel vaccine adjuvants and delivery systems. He has published over 190 scientific articles, is on the editorial boards of Expert Opinion on Biological Therapy and Human Vaccines, and serves on several external advisory boards. He is currently Global Head of External Research at Novartis Vaccines & Diagnostics, responsible for identification and assessment of new opportunities for collaborative research.
Abstract:
Vaccines are without a doubt the most successful of mankind’s medical interventions. However, despite more than two centuries of effective use of vaccines, many substantial challenges remain. These include: 1) improvement of existing but suboptimal vaccines (e.g., tuberculosis, influenza), 2) discovery and development of new vaccines against targets to address large unmet medical needs (e.g., HIV, malaria, cancer), and 3) rapidly responding to new pathogens (e.g., newly emerging microbes, bioweapons). Advances in these areas will require the application of new technologies and paradigms in the areas of antigen identification and optimization, novel potent and safe adjuvants, and enhanced vaccine delivery systems.






Yuzhang Wu

Third Military Medical University
China

Title: Mimogen-a new strategy for post-exposure vaccine development
Biography:
Yuzhang Wu has completed his Ph.D for Immunology at the age of 29 years from Third Military Medical University School of Medicine. He is the director of the Institute of Immunology, PLA, the Chair of National Engineering Lab for Vaccine Development of China and National Center for Immunoproducts Research and Development of China. He has published more than 150 papers in reputed journals, applied for 75 international and national invention patents, among which 43 has been approved; and has gained 2 item of Computer software copyright. He is serving as chief-editor of Immunological Journal
Abstract:
Although mass inoculation with preventive vaccines have drastically decreased the prevalence of hepatitis B virus (HBV)infection in a few countries, the pool of post-exposure population worldwide remains essentially unchanged. Therapeutic vaccine is a potentially promising means for the treatment of chronic hepatitis B in clinic, yet no is available at present. εPA44 is a de novo designed mimogen that acts as a tri-epitope integrated immunogen in order to prime therapeutic immunity while avoiding harmful and unnecessary immunity. To prove the mimogen concept, we performed a randomized, dose–escalation trial in 56 normal healthy research volunteers and a randomized, double–blind, placebo–controlled trial in 46 patients in two centers in China. εPA44 was well tolerated and safe in all participants, and induced designed immune responses that included vigorous HBV-specific CTLs, anti-Pre-S(2) antibodies, Th1 cytokines, and downregulated regulatory T cells. εPA44 might also decrease serum viral load of HBV and conduce serum HBeAg/HBeAb seroconversion in patients, which could persist to week 252 without relapse. Our findings highlight the potential of mimogen strategy for treating patients with chronic infections.






Pamuk Bilsel

FluGen, Inc.,
USA

Title: M2SR, a robust flu vaccine with long-lasting, cross-protective immunity
Biography:
Pamuk Bilsel, Ph.D. is Chief Scientific Officer at FluGen, Inc. Prior to joining FluGen as head of Research and Development, she was at Pharmexa-Epimmune developing DNA vaccines based on cell mediated immunity against influenza and malaria. At Pentamer Pharmaceuticals, she developed subunit vaccines against respiratory syncytial virus using virus-like particle technology. Preceding that Dr. Bilsel worked at Aviron generating live attenuated influenza vaccine strains in addition to studies with the cold-adapted influenza vaccine which was eventually launched as MedImmune’s FluMist®. Dr Bilsel’s post-doctoral training was at St. Jude Children’s Research Hospital with Dr. Yoshihiro Kawaoka.
Abstract:
Influenza (flu) virus causes a respiratory disease resulting in over 200,000 hospitalizations and ~ 36,000 deaths per year in the US Flu vaccines have remained virtually unchanged for decades. Despite the annual update of the three hemagglutinin (HA) vaccine antigens to match the circulating influenza strain, current vaccine efficacy is estimated to be ~60% across the population as a whole and much less for the elderly. Flu vaccine protection is sub-optimal and substantially lower than for most routinely recommended vaccines. The low efficacy rates are due primarily to the relatively poor immune response provided by both inactivated and live vaccines. There is an urgent need for highly protective flu vaccines that provide broad-spectrum immunity across all segments of the population.
FluGen has developed a new vaccine, M2SR (Single Replication), which exploits the best features of both inactivated and live attenuated influenza vaccines. Like the inactivated vaccine, it elicits a strong humoral response against the major neutralizing antigen, the HA. Similar to the live attenuated influenza vaccine, it is administered intranasally to mimic a natural infection and induce broad-spectrum immunity including mucosal and cell-mediated responses. The novelty of M2SR is that the vaccine virus presents multiple antigen targets to the immune system like a wild-type virus and activates the immune system without production of progeny virus. We have shown that the M2SR vaccine provides broad-spectrum, long-lasting cross-protection against multiple influenza subtypes including H5N1 in mice and ferrets.






Lucyna Cova

INSERMU
France

Title: In vivo electroporation for improvement of therapeutic DNA vaccine against chronic hepatitis B infection
Biography:
Lucyna Cova obtained her Ph.D in Biochemistry at the University Claude Bernard in Lyon, France. She held a post-doctorate position at the Wistar Institute in Philadelphia. Thereafter she joined Institut National de la Sante et Recherche Medicale (INSERM), which is a French medical research institute (equivalent of NIH). Currently she is a research Director at INSERM and a co-leader of a team working on Novel approaches against Hepatitis B and C infectionsat Cancer Research Center of Lyon. Lucyna Cova has expertise in viral hepatitis. Over the past decade her research focused on the development of therapeutic DNA vaccines against chronic hepatitis B.
Abstract:
Despite the existence of an effective prophylactic vaccine, chronic hepatitis B virus (HBV) infection remains a major public health problem. DNA-based vaccination has emerged as promising immunotherapeutic approach against chronic hepatitis B, although its efficacy needs to be increased as indicated by the results of first clinical trials. In this regard in vivo electroporation (EP)-mediated delivery appears of particular interestto improve therapeutic potency of DNA vaccines against chronic viral diseases. However, little was known of the ability of EP to improve DNA vaccine for therapy of chronic hepatitis B infection. We exploredEP-mediatedDNA vaccine delivery for hepatitis B immunotherapy using the duck HBV (DHBV) infection model, which is a reference for novel anti-HBV approaches evaluation. We first demonstrated in naïve animals that EP was able to dramatically enhance neutralizing potency of DNA vaccine leading to highly neutralizing, multi-specific B-cell response at clinically feasible DNA dose.Next, the therapeutic benefit of EP-mediated DNA vaccine delivery was investigated. The therapy of chronic DHBV-carrier ducks with EP-delivered DNA vaccine encoding viral proteins (envelope, core) and IFN- resulted in a marked and sustained decrease in viremia titers as compared with standard needle DNA injection. Importantly, a significant decrease in intrahepatic covalently closed circular viral DNA (cccDNA) form, responsible for chronicity of infection, was observed following EP of DNA vaccine. In addition a break of immune-tolerance was observed after DNA vaccine administration by EP. Collectively, our data indicate that electroporation is able to dramatically enhance therapeutic potency of DNA vaccine targeting hepadnaviral proteins supporting clinical application of this approach against chronic hepatitis B.






Bernadette Ferraro

University of Pennsylvania College of Medicine
USA

Title: A Synthetic Multi-Antigen Approach Targeting Plasmodium falciparum Malaria
Biography:

Abstract:
P. falciparum (Pf) malaria remains a significant public health problem. Current evidence suggests a vaccine candidate that elicits humoral and cellular responses to multiple sporozoite and liver-stage antigens may be able to confer protection against Pf malaria. Here, we report the preclinical assessment of a DNA vaccine approach that targets four Pf antigens: CSP, LSA1, TRAP, and CelTOS (MAV4). Synthetic DNA sequences were designed and delivered using electroporation (EP). In mice, DNA+EP delivery induced robust cellular and humoral immune responses. Further, hepatic CD8+ T cells produced antigen-specific IFNγ. A chimeric Pf-Plasmodium berghei (Pb) CSP sporozoite challenge model, a Pb sporozoite that contains Pf CSP in place of Pb CSP, was used to evaluate if immune responses induced by the Pf CSP component of MAV4 could decrease liver-stage parasite burden. Immunization with the synthetic pDNA Pf CSP resulted in a significant decrease in liver-stage levels. In Rhesus macaques, MAV4 elicited robust antibody and T cell responses to all antigens. Notably, the phenotype of the majority of antigen-specific CD8+ T cells indicated potential for cytotoxic and effector functions. In conclusion, DNA+EP delivery elicits strong immune responses against multiple malaria antigens and merits further study in clinical trials.






Birgitta Henriques-Normark

Karolinska Institute
Sweden

Title: Pneumococcal infections and vaccination
Biography:
Birgitta Henriques Normark is professor and head physician in Clinical microbiology at Karolinska Institutet and Karolinska University hospital, as well as head physician at the Public Health Agency of Sweden.She is also vice dean for recruitment at Karolinska Institutet and a board member of the Swedish Research Council, Medicine and Health.Her research focuses on epidemiology, antibiotic resistance and host-microbe interactions in bacterial infections with special focus on pneumococcal epidemicity, molecular epidemiology, and mechanisms of invasive disease, innate immunity and host-microbe interactions determining disease outcome. The research has been published in 136 publications of which 107 are original peer reviewed articles.
Abstract:
Pneumococci are major contributors to morbidity and mortality worldwide. They are the major cause of milder respiratory tract infections such as otitis and sinusitis, but also to more severe invasive infections such as community-acquired pneumonia with associated septicemia and meningitis. Even though being a devastating pathogen, pneumococci are also common colonizers of the upper respiratory tract of healthy children where from they may spread to cause disease. Risk groups for acquiring an invasive pneumococcal infection (IPD) include preschool children and the elderly, as well as immunocompromised individuals, splenectomised, and patients with a previous influenza virus infection. Several bacterial virulence factors have been described for pneumococci of which a major one is the capsular polysaccharide. Depending on differences in these capsular structures so far more than 90 different serotypes have been distinguished. Recently so called conjugated vaccines (PCV) have been introduced into the child hood vaccination program in many countries. These vaccines are based on a limited amount (7, 10 or 13) of the capsular serotypes. In Sweden PCVs were introduced in the whole of Sweden year 2009. Vaccine introduction has led to a reduction in the incidence of IPD in vaccinated children but also to serotype replacementand an increase of non-vaccine type disease.






Kar Muthumani

University of Pennsylvania School of Medicine
USA

Title: Synthetic enhanced EP delivered Ig plasmid vector drives biologically relevant anti-HIV-1 envelope responses in vivo
Biography:
Dr. Muthumani received his MS with honors from the Madurai Kamaraj University, India. He received his Ph.D. in Molecular Biology from the School of Biological Sciences, Madurai Kamaraj University, India in 1995 and completed his postdoctoral training at the Texas A&M University and University of Pennsylvania School of Medicine, PA, USA. He has been Research Assistant Professor at the Dept. of Pathology and Lab. Medicine, University of Pennsylvania, Philadelphia, PA since 2008.
His research interests focus on the development of novel DNA vaccines and therapeutics against emerging infectious diseases using enhanced DNA technology and electroporation (EP) delivery techniques and comparing their ability to drive immune responses with previously developed immunogens for HIV, Dengue, Chikungunya virus and Middle Eastern Respiratory Syndrome (MERS) virus. Further, his recent research focus has been on the generation in vivo of DNA plasmid-encoded neutralizing antibodies (NAbs) in order to generate passive immunity against select pathogens. Using highly optimized DNA construct designs and delivery methods, we are studying the ability of our plasmids to actively drive immune responses or passively provide protection against viral disease. He has published more than 52 publications in widely recognized peer-reviewed journals, including first-author publications in Nature Cell Biology, Blood, JBC, JI and PLoS. A large percentage of his work can be characterized as translational research due to its immediate clinical relevance. Furthermore, his work has been awarded a total of 15 patents, the majority of which are licensed and provide royalties to the University as well as the department.
Abstract:
Background: Monoclonal Ab’s have demonstrated therapeutic utility against several malignancies and infectious diseases. A drawback of this strategy is the time-consuming and expensive process requiring purification and scale up production of the Ab’s for clinical use. A method to produce antibodies in vivo would be significant improvement for this platform. It would be important if these Ab’s could be administered with out induction of vector serology allowing repeated administrations. Furthermore, delivery in a non-permanent fashion would also have advantages.
Methods: Here we report development of new synthetic optimized plasmid vector/improved EP encoding Abs genes for delivery in vivo. This strategy allows for in vivo synthesis and serum expression of such ex vivo developed antibodies. The antibodies were found to be expressed in the blood as well as in other compartments and were functional and at protective levels for model systems.
Results: An “enhanced and optimized” DNA plasmid generates immunoglobulin heavy and light chains (Fab) of an established neutralizing anti-HIV monoclonal antibody (VRC01). We demonstrate that the serum of transfected animals exhibited the ability to bind to HIV envelopes in ELISA and FACS analysis against diverse isolates and this serum possessed HIV neutralizing activity equivalent to the “native” VRC01 antibody in vivo. In vivo delivery seroconverted the animals with in a few hours and neutralizing activity lasted for weeks. This technology has important advantages for in vivo antibody production which could compliment or circumvent the need for standard antigen based vaccination, particularly in situations where there is difficulty in generation of protective antibody responses by immunization.
Conclusion: This is the first study we are aware of using synthetic DNA plus EP delivery to produce circulating bioactive antibody responses in a living animal. The study has implications for prophylactic and therapeutic strategies for HIV and other important diseases.






Michael Hust

Technische Universität Braunschweig
Institut für Biochemie, Biotechnologie und Bioinformatik
Germany

Title: A vaccine pipeline: using phage display for identification of immunogenic proteins and generation of human antibodies for diagnostics and therapy
Biography:
Michael Hust studied biology at the Carl von Ossietzky Universität in Oldenburg, Germany, from 1993-1999. He got his PhD at the Leibniz Universität in Hannover, Germany, in 2002. Since end of 2002 he is working as group leader at the Technische Universität Braunschweig, Germany, in the department of biotechnology. In 2011 he finished his professorial dissertation (Habilitation, venia legendi for Biotechnology) and was appointed as Privatdozent (PD). He published more than 70 articles (including book chapters and reviews) on antibody engineering and phage display. He cofounded the mAb-Factory GmbH in 2007 and the Yumab GmbH in 2012. He is working on the development of human and human-like antibodies for diagnostics and therapy. Another field of work is the identification of immunogenic proteins of pathogens using phage display.
Abstract:
The identification of new immunogenic proteins of pathogens is a prerequisite for development of vaccines and diagnostic assays. We are using phage display to identify novel antigens from bacterial genome libraries. We also developed an antibody generation pipeline. The combination of both phage display based technologies led to a “vaccine development pipeline”. Here, the technology will be described and examples for the identification of immunogenic proteins of Mycoplasma species and Salmonella Typhimurium as well es examples from our antibody generation and engineering pipeline for pathogens and toxins (botulinum toxins, venezuelan equine encephalitis virus) will be given.






Vega Masignani

Novartis Vaccines and Diagnostics
Italy

Title: Defeating meningococcal disease: from a glycoconjugate vaccine against MenACWY to a protein-based vaccine against Meningococcus B.
Biography:
Vega Masignani joined Chiron Vaccines (now Novartis Vaccine and Diagnostics) division in Siena in 1995. She got her PhD in Biotechnology in 2000 and since then she has always worked in the Research Department. She was involved in the Meningococcus B vaccine project since the very beginning and participated in the identification of the protein candidates that are today included in the recently licensed Bexsero vaccine. From 2005 to 2010 she has worked as Project Leader of the Streptococcus pneumoniae vaccine project and has contributed to the identification and characterization of the pneumococcal pilus, an important factor involved in bacterial pathogenesis. Since 2010, she is Project Leader of the MenB project and is responsible for all the activities that are carried out in Research to further elucidate the role of the Bexsero antigens.
Abstract:
Neisseria meningitidis is the leading cause of meningitis and sepsis in children and adolescents. Based on the chemical composition of the capsular polysaccharide, N. meningitidis can be distinguished into 12 serogroups, however >95% of disease cases are caused by 5 serogroups (MenA, B, C, W and Y). The first vaccine against meningococcal disease was based on the conjugation technology, where the MenC capsular polysaccharide was conjugated to a carrier molecule. This vaccine was highly efficacious and contributed to reduce the burden of disease in UK, where it was first introduced, and in all the other countries where it was later implemented. Following this success, the same approach was applied to serogroups A, W and Y and a multicomponent MenACWY vaccine was developed. This strategy was not feasible for serogroup B and therefore a broad spectrum vaccine against meningococcus B has long remained elusive. An innovative approach, termed Reverse Vaccinology was coined in early 2000 and applied to MenB with the aim to identify sub-capsular antigens for the development of a universal vaccine against this important serogroup. Potential candidates were selected and used for the generation of the multi-component vaccine formulation termed 4CMenB, recently licensed in Europe with the commercial name of Bexsero. 4CMenB is composed of three recombinant protein antigens (Factor H binding protein fHbp, the Neisserial Heparin binding antigen NHBA and the Neisserial adhesin A NadA) plus purified outer membrane vesicles (OMV) of the epidemic New Zealand strain. 4CMenB has been shown to be highly immunogenic in human subjects of different age groups and holds the promise for the elimination of this devastating disease.






Phil Sutton

Royal Children’s Hospital
Australia

Title: Heat shock protein complex vaccines against mucosal pathogenic bacteria
Biography:
Phil Sutton completed his PhD in Immunology at Manchester University in 1991 and has worked on vaccine research for almost 20 years, mostly in Australia. This includes academic post-doctoral positions in Universities and research institutes, and as an industry group leader working on vaccine R&D. Of his 64 peer reviewed publications, 32 are vaccine-related. He is also internationally recognised in the field of Helicobacter pylori pathogenesis. Phil is currently head of the Mucosal Immunology Research group at the Murdoch Childrens Research Institute in Melbourne.
Abstract:
Heat shock proteins (Hsp) are highly conserved molecules with a range of functions, including acting as chaperones for cellular proteins and the ability to activate innate immune receptors. Hsp complex (HspC) vaccines, containing Hsp derived from pathogenic bacteria, are immunostimulatory without an exogenous adjuvant and induce immunity against their chaperoned bacterial proteins. HspC adjuvanticity is believed due to the ability of Hsp to activate toll-like receptors, though this has not been thoroughly examined. Further, the application of this vaccine technology against mucosal pathogens has not previously been explored. RESULTS: Helicobacter pylori infect the stomach and are the major aetiological factor in gastric cancer. Vaccination of mice with H. pylori HspC without exogenous adjuvant produced equivalent protection, and notably increased local cytokine levels but less inflammation, as similar adjuvanted vaccines. This is the first demonstration that HspC vaccines can induce protective immunity against a mucosal pathogen without a mucosal adjuvant. Neisseria meningitides colonise the nasopharynx and in some individuals, invade the host causing meningococcal disease, including meningitis. Vaccination of mice with N. meningitides B HspC induced a strong immune response. Using MyD88-/- mice, we examined the importance of TLR signalling in the HspC mechanism of action. While the immune cytokine response was dependent on MyD88, antibody induction occurred completely independently of MyD88. CONCLUSION: HspC provide an effective vaccine strategy against mucosal pathogenic bacteria without the requirement for a mucosal adjuvant. While induction of a cellular response involves TLR signalling, the generation of humoral immunity occurs via a different, TLR-independent, mechanism.






Zakaria Hmama

University of British Columbia
Canada

Title: Upgrading the 100 year-old BCG vaccine
Biography:
Zakaria received a PhD degree from the University Claude Bernard (Lyon, France) in 1993. He is currently Associate Professor at the University of British Columbia (Department of Medicine) and holds a Scholarship Award from the Michael Smith Foundation of Health Research. Ongoing research in Zakaria’s lab focuses on developing novel gene manipulation technologies to upgrade the current BCG vaccine in order to maximize the induction of protective TB immunity. Of equal importance to the vaccine project, a biology-based study of Mtb persistence has revealed important virulence factors that represent attractive drug targets that could be used for TB treatment
Abstract:
The increasing spread of drug-resistant M. tuberculosis (Mtb) strains is dramatically impacting upon tuberculosis (TB) control programmes. Therefore many health authorities came to the conclusion that efficient preventive vaccination would be the best cost-effective strategy to stop the spread of all form of TB, especially in developing countries. The current vaccine M. bovis BCG (developed in early 1900's) is proven to protect efficiently newborns…unfortunately, its efficacy wanes as kids age. Therefore, many investigators are focusing their efforts towards upgrading the 100 year-old BCG. We have been investigating the underlying mechanisms behind the inefficacy of BCG for the last five years. We found that BCG, although safe and non pathogenic for human, mimics many pathogenic features of Mtb. In particular we found that BCG blocks macrophage (MØ) apoptosis and phagolysosome fusion, which are essential innate responses that restricts bacterial persistence and also initiate adaptive immune response. We recently developed a strategy to convert BCG into a strong proapoptotic strain that induces MØ apoptosis and accelerate phagolysosome fusion. The reshaped BCG also induces the shedding of apoptotic blebs, which cross-prime dendritic cells for antigen presentation to T cell, a novel mode of antigen presentation called the “detour pathway”. Current research efforts in this lab are focusing on upgrading further proapoptotic BCG to express TB10.4 and VAPB47, which are major protective Mtb antigens not expressed in conventional BCG. We strongly believe that this novel approach will generate a novel TB vaccine highly competitive to those currently under evaluation in clinical trials.






Alexandre M. Vieira Machado - Fiocruz

Rene Rachou Research Center
Brazil

Title: Immunization with neuraminidase deficient influenza virus is highly immunogenic and non-pathogenic to wild type and immunocompromised mice
Biography:
Alexandre Vieira Machado is graduated in Pharmaceutical Sciences by Federal University of Minas Gerais (UFMG), Brazil (1994), where he also obtained his master degree in Microbiology (1998) . Further, he obtained his PhD in Microbiology at Pasteur Institute, Paris, France, where he started his studies about the reverse genetics of influenza A virus, mostly focusing on development of recombinant influenza viruses as antigen delivery vectors against human and veterinary diseases. He is currently Associated Researcher at Oswaldo Cruz Foundation, Brazil and his studies are mainly focused on the development of vaccines against protozoan disease using influenza vectors and inflammatory responses triggered by influenza virus.
Abstract:
Recombinant influenza viruses are promising viral platforms to be used as antigen delivery vectors. To this aim, one of the most promising approaches consists to generate recombinant viruses harboring partially truncated neuraminidase (NA) segments. To date, all studies have been pointed to safety and usefulness of this viral platform. However, some aspects of the inflammatory and immune responses triggered by those recombinant viruses and their safety to immunocompromised hosts remained to be elucidated. In the present study, we generated a recombinant influenza virus harboring a truncated NA segment (NA-Δ) and evaluated the innate and inflammatory responses and the safety of this recombinant virus to wild type or knock-out (KO) mice with impaired innate (Myd88 KO) or acquired (RAG KO) immune responses. Our results showed that recombinant influenza virus harboring truncated neuraminidase segment abrogated lung and systemic inflammatory response in wild type mice and were completely harmless to KO mice. We also demonstrated that vNA-Δ infection could prevent unbalanced cytokine production that strongly contributes for lung damage in infected mice. In addition, the recombinant influenza virus was able to trigger both local and systemic virus specific humoral and T CD8+ cellular immune responses which protected immunized mice against the challenge with a lethal dose of homologous A/PR8/34 influenza virus. Taking together, our findings indicate that the neuraminidase deficient virus results in mild lung inflammation, induces a strong protective immunity against influenza challenge and are safe even to immunocompromised hosts.






Daniela Chessa

Sassari University School of Medicine
Italy

Title: Characterization of different antigens in Salmonella Abortusovis for developing a vaccine
Biography:
Daniela Chessa has completed her PhD in the University of Pisa on the 2005 in Microbiology and Genetic. Her doctorate research was on the effects of the expression of a capsule in Salmonella Typhi. This work was done in the laboratory of Prof. Andreas J. Baumler, Texas. In 2005-2009, she was working like a post doctoral position with Prof. Andreas J. Baumler, California. She studied the effects of the fimbrial in Salmonella Typhimurium and Salmonella Typhi with experiments in vitro and in vivo. Now she is working at the Molecular Biology Lab with Prof. Salvatore Rubino, Italy .
Abstract:
The majority of the more than 2,500 known Salmonella serovars cause gastroenteritis in humans, a localized infection characterized by acute intestinal inflammation, diarrhea and fever. Bacterial invasion and survival in host cells in the intestine lead to stimulation of the innate immune system, which results in the massive intestinal inflammatory response that characterizes Salmonella-induced gastroenteritis. Some Salmonella serovars are host restricted and cause systemic infections that differ dramatically in their clinical presentation from gastroenteritis. S. Abortusovis is a sheep-adapted pathogen, which does not infect humans. Translocation of bacteria from the intestinal lumen into the lamina propria is detected by the immune system through patter-recognition receptors including TLRs that are able to recognize microbe associated molecular patterns (MAMPs). Lipopolysaccharide, a conserved MAMPs present in the outer membrane of Gram-negative bacteria, is a potent agonist of the TLR4-MD-2-CD14 receptor complex and bacterial flagellin is a MAMP recognized by TLR5. Limited information is available about the immune response of sheep to S. Abortusovis and the interactions of this moleculars and the TLRs specific. The goal of our study is to characterize virulence mechanisms of S. Abortusovis and with this informations the development of novel strategies for treatment of infection like a vaccine.






Pier Luigi Cherchi

Sassari University
Italy

Title: P16 immunostaining and hpv testing in histological specimens from uterine cervix
Biography:
Prof. Pier Luigi Cherchi has completed his M.D. at the age of 23 years from Sassari University and postdoctoral studies from Sassari University, Italy. He is the director of Chair of Gynecologic Oncology at Sassari University. He has published more than 500 papers in international Gynecologic journal.
Abstract:
Background: The cellular tumor suppressor protein p16INK4a (p16) has been identified as a biomarker for transforming HPV infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression.
Objective: To confirm the role of P16 as biomarker for transforming HPV infections.
Methods: 56 biopsies of the cervical canal collected from january 2012 to september 2012 in the Institute of Pathology of Sassari University. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) Histology Kit (Dako Cytomation).
Results: In 56 biopsies performed in women aged between 23 and 69 years we highlighted, by histological analysis, 24 cases of low-grade lesions (LSIL-CIN1) and 31 cases of high-grade lesion (HSIL-CIN2/3); 15 CIN2, 14 CIN3 and 2 cervical Squamous cell Carcinoma in Situ (SCIS). One case was an Infiltrating Squamous cell Carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in cases CIN3 (14), and 3 carcinomas the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%.
Conclusions: We have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a great ability to identify the viral infection.






Andreas Meinke

Valneva Austria GmbH
Austria

Title: Design and evaluation of a novel OspA-based vaccine for the prevention of Lyme borreliosis
Biography:
Andreas Meinke obtained his Ph.D. in 1992 from the University of Freiburg and the University of British Columbia in Vancouver, Canada. Subsequent to his work at UBC, he moved to the Department of Microbiology and Genetics, University Vienna, as an Assistant Professor. In 1998, he joined the newly founded biotech company Intercell AG, now Valneva Austria GmbH. At present he is responsible at Valneva for pre-clinical and translational research. Andreas Meinke has authored and co-authored more than 60 publications, lectured in several University programs and filed more than 20 patents in the field of antigen discovery and vaccine development.
Abstract:
At present, there is no vaccine available to prevent Lyme borreliosis in humans, although it has been shown that the disease can be averted by immunization with an OspA based vaccine (LYMErix™). In Europe three Borrelia species, B. afzelii, B. burgdorferi and B. garinii are the main pathogens causing Lyme borreliosis, the most common tick-borne zoonosis. Outer surface protein A (OspA) is one of the dominant antigens expressed by the spirochetes when present in the tick vector. The various pathogenic Borrelia species express different OspA serotypes on their surface: B. burgdorferi (serotype 1), B. afzelii (serotype 2), B. garinii (serotypes, 3, 5 and 6) and B. bavariensis (serotype 4). In order to target these Borrelia species, we have designed a multivalent OspA-based vaccine. The vaccine includes three proteins, each containing the C-terminal half of two OspA serotypes linked to form a heterodimer. In order to stabilize the C-terminal fragment and thus preserve important structural epitopes, disulfide bonds were introduced and the immunogenicity increased by addition of a lipidation signal. Active immunization with the adjuvanted Lyme borreliosis vaccine protected mice from a challenge with spirochetes expressing either OspA serotype 1, 2 or 5, using infected ticks or in vitro grown bacteria as a challenge. Further immunological analyses (ELISA, surface binding and growth inhibition) indicated that the vaccine can provide protection against the majority of human pathogenic Borrelia species. This rational designed OspA-based vaccine is therefore suitable for global prophylaxis of Lyme borreliosis.






Tjip van der Werf

University of Groningen
The Netherlands

Title: Therapeutic vaccines for drug-resistant tuberculosis
Biography:
Tjip van der Werf completed his PhD Thesis on TB and M. ulcerans disease in Ghana in 1991, when he trained as a pulmonary physician. After having worked in Intensive Care, he resumed studying mycobacterial infections – especially, drug treatment-related studies – after having obtained research funding from various sources, including Dutch government and EU grants. His current research includes PK/PD studies in MDRTB and clinical studies both in the Netherlands as well as in high endemic regions in Eastern Europe and Asia, and in M. ulcerans infection in West Africa. He was appointed as a Professor in Infectious Diseases at the University of Groningen, the Netherlands.
Abstract:
Despite impressive advances in the last decades, TB control has been jeopardized by a staggering emergence of drug-resistant, and especially, multidrug-resistant (MDR)TB. Collapsing TB services and poor adherence to principles of TB management have facilitated the emerging epidemic of MDRTB. Novel TB drugs now reaching the market. Still, without vaccines, the current global TB epidemic, and the goal set by the World Medical Association to eradicate TB by the year 2050, remains unattainable. BCG, the only currently available TB vaccine, provides limited protection, but does not impact on TB transmission. Therefore, novel TB vaccines are needed. Of over 70 products are currently in the pipeline to be developed for possible use as TB vaccine, only five products were identified to enter clinical testing for possible use as a immuno-therapeutic product. Such products may shorten, and perhaps enhance efficacy, of MDRTB treatment. Current MDRTB treatment lasts up to 20 months with drugs that have important adverse effects, and successful outcome is currently only 50-60%. MDRTB therefore provides an ideal platform for testing these candidate therapeutic vaccine products. Studies to evaluate these products may require novel, innovative study designs. Our group is currently embarking on studies to evaluate two of these products in patients with MDRTB.






Yasuhiro Yasutomi

Tsukuba Primate Research Center
Japan

Title: Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization
Biography:
Dr. Yasuhiro Yasutomi was a Research fellow (Immunology), 1990-1991. at Harvard Medical School from 1990-1991 and then Instructor 1992-1994. He was Instructor in Medicine at Department of Viral Pathogenesis in Beth Israel Hospital in Harvard Medical School from 1994-1996. He was associate professor in Mie University Graduate School of Medicine from1996-2007. He is Director at Tsukuba Primate Research Center in National Institute of Biomedical Innovation, and Professor in Mie University Graduate School of Medicine in July 2007 to present. He is an immunologist in vaccine development field.
Abstract:
Viral vectors are promising vaccine candidates for eliciting suitable Ag-specific immune response. Since Mycobacterium tuberculosis (Mtb) normally enters hosts via the mucosal surface of the lung, the best defense against Mtb is mucosal vaccines that are capable of inducing both systemic and mucosal immunity. Although Mycobacterium bovis bacille Calmette-Guérin is the only licensed tuberculosis (TB) vaccine, its efficacy against adult pulmonary forms of TB is variable. In this study, we assessed the effectiveness of a novel mucosal TB vaccine using recombinant human parainfluenza type 2 virus (rhPIV2) as a vaccine vector in BALB/c mice. Replication-incompetent rhPIV2 (M gene-eliminated) expressing Ag85B (rhPIV2-Ag85B) was constructed by reverse genetics technology. Intranasal administration of rhPIV2-Ag85B induced Mtb-specific immune responses, and the vaccinated mice showed a substantial reduction in the number of CFU of Mtb in lungs and spleens. Unlike other viral vaccine vectors, the immune responses against Ag85B induced by rhPIV2-Ag85B immunization had an advantage over that against the viral vector. In addition, it was revealed that rhPIV2-Ag85B in itself has an adjuvant activity through the retinoic acid-inducible gene I receptor. These findings provide further evidence for the possibility of rhPIV2-Ag85B as a novel TB vaccine.






Ursula Wiedermann

Medical University of Vienna
Austria

Title: Vaccination in risk groups with special focus on non-responsiveness to routine vaccines
Biography:
Univ. Prof. Dr. Ursula Wiedermann had studied Medicine in Vienna, Austria. Between 1990-1995 she completed her PhD thesis in Sweden at the Institute of Clinical Immunology at the University of Gothenburg. Back in Vienna she continued her research career at the University of Vienna concentrating on mucosal vaccination against allergic diseases. After her habilitation (venia docendi) in 1999 she founded the research group “Mucosal Immunity and Vaccination”. In 2001 she finished her medical training as specialist for “Immunology” and “Specific Prophylaxis and Tropical Hygiene”. At the Institute of Specific Prophylaxis and Tropical Medicine she enlarged her research areas to vaccine development against infectious diseases, allergies and cancer, and focused on clinical vaccine trials to study immune responsiveness and immune failures upon vaccination. In 2004 she became Head of the Institute of Specific Prophylaxis and Tropical Medicine and in 2006 she was assigned Professor for Vaccinology at the Medical University Vienna. She is member of the Austrian Supreme Board of Health and since 2011 chair of the Austrian Advisory Committee for Immunization Practice of the Austrian Ministry of Health. She has more than 100 publications in peer reviewed journals and is frequently giving presentations at international and national conferences.
Abstract:
Worldwide vaccination programs against the most prevalent vaccine preventable diseases have been introduced by the health authorities to reduce morbidity and mortality rates, minimize disease outbreaks, and ultimately eradicate diseases. These recommendations are based on clinical trials performed in selected, healthy populations. The situation is unlike for patients with different chronic diseases and/or immunodeficiencies, since there is a lack of prospective randomized studies. Consequently, the vaccination recommendations are primarily based on theoretical considerations and are often quite imprecise, leading to suboptimal vaccine preventive care. Within the last years we concentrated our research programs on the immunological characterization of non-responsiveness to routine vaccines in healthy as well as different risk groups. Non-responsiveness in healthy individuals occurs in 2-10% of vaccinees and is defined by a lack of sufficient protective immune-responses after primary or booster vaccination. We could demonstrate that non-responsiveness to tick-borne encephalitis vaccine is associated with both, low humoral and cellular antigen-specific immune responses. In genetically pre-disposed hepatitis B non-responder, showing an association to certain HLA-DR subtypes, high IL-10 levels as well as increased regulatory T and B cells are linked to non-responsiveness to hepatitis B but also to other vaccine antigens. Immunosenescence is another risk factor for non-responsiveness to vaccination. With increasing age (> 60 yrs) humoral and cellular responses are significantly lower, particularly to novel vaccine antigens, than in younger vaccinees and thus associated with increased infection susceptibility. We recently described that primary vaccination with Japenese encephalitis vaccine led to humoral and cellular non/low responsivenss in 47% of the vaccinated elderly. The frequency of regulatory T cells as well as late differentiated effector memory cells was significantly higher compared to the young vaccinees and this was associated with increased CMV-seropositivity. This study indicated that elderly may require different vaccination strategies, modified booster schedules and other adjuvants systems for vaccines, while primary vaccination should be encouraged to be done before the age of 60. Similar studies are now being performed in allergic patients and obese individuals, since their immunological status seems to be impaired as well and the effectiveness of vaccination is currently unclear. Along these lines, a multicentre study on vaccination of cancer patients is on the way to answer important questions, such as the influence of tumor entity, stage of diseases and chemotherapy on vaccine responsiveness. Thus, based on the obvious need for significant and solid data on vaccine responsiveness in diseased subjects, such studies will provide evidence for improved vaccination recommendations and specific vaccination strategies in the different risk groups of growing incidence with global impact on health systems and medical care.






Latifynia Afshineh

Tehran University of Medical Sciences
Iran

Title: Post challenging effects of new formulation of leishmania major antigen in Balb/c mice
Biography:

Abstract:
Background/Purpose: Cutaneous leishmaniasis (CL) is a zoonotic disease transmitted between rodents and canines, mainly induced by phelebotomus sand flies. In southern of Iran, the incidence of this protozoan disease has doubled over the last decade. Human leishmaniasis is distributed worldwide, but mainly in the topics and subtropics, with a prevalence of 12 milion cases and an approximated incidence of 0.5 milion cases of VL and 1.5 milion cases of cutaneous leishmaniasis (CL) . The aim of this study was comparing the protective effects of a candidate cocktail vaccine encoding various leishmania major antigens in highly susceptible (Balb/c) mice after challenge with live leishmania. In this regards we selected two previous study’s successfull doses (100 & 200 μg/o.1ml), three injection groups : Leishmania plus BCG (LB), Leishmania plus Teucrium Polium as a new adjuvant [LT], leishmania plus BCG and Teucrium Polium (LBT),and one type susceptible mice(Balb/c) which measured expansion of white pulp size after challenge with live leishmania.
Methods: A new formulation antigen evaluated in susceptible mice (Balb/c).Leishmania major promastigotes which cultured and harvested at different growth stagesThese harvested organisms modified and combined of five different methods to produce cocktail crud Antigen antigen. It was tested for sterility and protein levelsmeasured by Lowry method. This crud antigen injected intradermally to Balb/c mice. We have one injection both two same booster doses with one week interval. After 20 days after third leishmania injection challenge or re-exposure was performed with live Leishmania. The protective response was evaluated by observation of inducing lesion, and progress of it or another critical signal, at least survival of injected mice for every week,over 70 days . After this all mice were euthanized with diethyl ether, their spleens removed and prepared Histological sections of them and stained with hematoxylin & eosin .After that expantion of spleeny white pulp (SWP) were studied microscopically.
Results: Our results show control group white pulps compared with others, have different structure and size. The SWP size increases is dependent on the injection group .There was a remarkable expansion of lymphoid follicles in the treated groups in Balb/c mice.
Conclusion: This new formulation antigen was able to stimulate and expand the lymphoid constituents of spleen tissue after challenge with live leishmania. The SWP is where immune responses and antibodies are produced .Therefore, the effect of antigen preparations on secondary immune responses, adaptive immunity, and antibody production is important in determining the susceptibility of mice to cutaneous leishmaniasis and the induction of immunity lead to protectivity encounter to challenge with live Leishmania major.






Rakesh Kumar

Serum Institute of India Limited
India

Title: Immunological studies on Tetanus Toxoid
Biography:
Dr. Rakesh Kumar gained his M.Sc. and M.Phil (Microbiology) from H.P. University, Shimla (India), later being awarded his Ph.D. in Biotechnology by University of Pune. In January 1982, he joined Central research Institute, Kasauli (H.P.) under Government of India, Ministry of health and Family welfare and worked till July 1994. Central Research Institute is a pioneer Institute for immuo-biological products, established in 1905. Central Drug Laboratory for biological products is also a part of the Institute, which is a National Control Laboratory and is also WHO recognized. He joined Serum Institute of India Limited in 1994 as manager and devoted his full time to the increasing success of Serum Institute culminating in his appointments in 1997 as Dy. Director (Production), Additional Director (Production) in 2003 and as Director in 2005. He has had full time, hands of experience in Scientific and Compliance Professional in various aspects of Bio-pharmaceutical industry , excellent knowledge & understanding of Research, Development and Production of Biologicals, International regulatory requirements, mentoring and coaching skills, exhaustive work for process–development, optimization, set-up, subsequent production and formulation of various mono-valent and combination vaccines.
Abstract:
Tetanus toxoid is one of the most successful vaccines used in immunization programme almost all over the world. Neonatal tetanus can be prevented by immunizing women of childbearing age with tetanus toxoid, either during pregnancy or outside of pregnancy. Tetanus vaccine is used either in mono or in combination with other antigens i.e. Diphtheria, Pertussis (whole cell or acellular), Hepatitis B, Haemophilus influenzae B, Inactivated polio vaccine etc. Tetanus toxoid is produced batch-wise using complex media, often containing poorly defined components. Therefore, batch related quality control to guarantee safety and potency is a statutory requirement. In the new concept, quality control is seen as an instrument to monitor consistency of the critical steps in the production process and testing of vaccines. Monitoring consistency places emphasis on in-vitro methods, since in-vivo tests are less appropriates (expensive, time consuming and inaccurate) for this purpose. Immunochemical techniques may include the use of polyclonal antibodies for direct ELISA or monoclonal antibodies in capture ELISA and immunoblotting to indicate local differences in antigenicity.






Srinivas Reddy

Serum Institute of India Ltd
India

Title: Process development and immunogenicity studies on a serogroup ‘X’ Meningococcal polysaccharide conjugate vaccine
Biography:
Srinivas Reddy did his Ph.D from Indian Institute of Technology, Chennai. He is working as a Senior Manager at Serum Institute of India Ltd (World's 5th largest vaccine manufacturer) . He has 15 years of industrial experience in research and development worked in major biotech companies in India. He has published international papers and also has process patents in the area of vaccine and therapeutic monoclonal antibody development.
Abstract:
Meningococcal serogroup X (MenX) is responsible for recent outbreaks of meningitis reported in sub-Saharan region of Africa. Although protective polysaccharide conjugate vaccines are available against serogroups A, C, Y and W but they are not effective against MenX. An efficacious, monovalent conjugate vaccine was designed against MenX and a fed-batch fermentation process was developed. The MenX polysaccharide (PS) was purified and yield estimated to be 15-fold higher than the reported elsewhere. Structure of MenX polysaccharide was confirmed by 1H, 13C NMR spectroscopy analysis. The MenX polysaccharide is a homopolymer of N-acetyl-D-glucosamine-4-phosphate residues held together by alpha (1-4) phosphodiester bonds without O-acetyl groups. Molecular weight of MenX polysaccharide was found to be 310 kDa using HPLC-SEC coupled to refractive index (RI) detector. The MenX–Tetanus toxoid (TT) monovalent conjugate proved to be highly immunogenic in mice, and the bactericidal titers of MenX–TT conjugate were 10-fold higher than native PS. Increasing the dose of MenX–TT conjugate from 0.5 μg to 1.0 μg induced an 8-fold higher antibody titer as well as serum bactericidal titer. The current work suggests that the MenX–TT conjugate is a candidate vaccine against meningitis caused by Meningococcal group X strains.






Gerardo Guillen

Centro de Ingenieria Genetica y Biotecnologia
Cuba

Title: Development of novel therapeutic hepatitis B vaccine
Biography:

Abstract:
Despite the existence of effective prophylactic vaccines, hepatitis B virus (HBV) infections remain a major public health problem. About 370 million people are chronically infected worldwide. Chronic hepatitis b (CHB) infection also increases the risk of liver diseases such as cirrhosis and hepatocellular carcinoma. Current antiviral therapies fail to control viral replication in the long term in most patients. As HBV persistence has been associated with a defect in the development of HBV-specific cellular immunity, therapeutic vaccination has been extensively studied in CHB. HBsAg-based vaccines, including prophylactic vaccines and HBsAg-based formulations with novel adjuvants have been used with unclear or negative results. The development of therapeutic vaccines against CHB requires proofing the capacity of the formulation to subvert a tolerated immune response. NASVAC as a new generation vaccine include the use of a novel immunization route (intranasal-IN) and a novel antigen (HBcAg) expressed in E. coli, used in a combined formulation with HBsAg. The evaluation in mouse support the rationality of the therapeutic vaccine candidate targeting the stimulation of CD4(+) and CD8(+) T-cell responses and the induction of pro-inflammatory cytokines capable of controlling viral replication. NASVAC proved to be immunogenic in mouse models and then in phase I, II and III, randomized, double blinded and placebo controlled clinical trials developed in healthy volunteers and CHB patients.






Yalena Amador-Canizares

Center for Genetic Engineering and Biotechnology
Cuba

Title: Induction of de novo HCV Core-Specific Cell-Mediated Immune Responses and Enhancement of Neutralizing Antibodies Response by CIGB-230, a DNA-Based Vaccine Candidate, on Triple Therapy with IFN-α plus Ribavirin
Biography:
Yalena Amador-Cañizares has completed her Ph.D at the age of 33 years from Havana University. She is a young investigator at the Hepatitis C Section, of the Vaccines Department, at the Center for Genetic Engineering and Biotechnology, a leading biotechnology institute at Havana, Cuba. She has published more than 10 papers in reputed journals. She is member of the Cuban Societies of Hepatology and Immunology. She has coauthored 4 Awards of the Cuban Academy of Sciences.
Abstract:
CIGB-230 is a vaccine candidate based on the mixture of a DNA plasmid, expressing HCV structural proteins, with recombinant HCV core protein. In this work CIGB-230 was administered in different schedules regarding IFN-α plus ribavirin therapy in a Phase II clinical trial. Paired serum and PBMC samples from baseline and end of treatment were analyzed. Data on virological and histological response and their association with immune variables are also provided. From week 12 to week 48, all groups of patients showed a significant reduction in mean leukocyte counts. Statistically significant decrements in antibody titres were frequent, but only individuals immunized with CIGB-230 as early add-on sustained the core-IgG response, and the neutralizing antibody response was enhanced only in patients receiving CIGB-230. Cell-mediated immune responses also tended to decline, but significant decrements in IFN-γ secretion and total absence of core-specific lymphoproliferation were exclusive of the control group. Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens. Importantly, it was demonstrated that the quality of CIGB-230-induced immune response depends on number of doses and timing of administration in relation to the antiviral therapy. Specifically, the administration of six doses of CIGB-230 as late add-on to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γ secretion, with a favorable impact in the virological response. In conclusion, CIGB-230, combined with IFN-α-based therapy, modifies the immune response in chronic patients. These evidences shed light in the design of more effective therapeutic vaccine interventions against HCV.






Xueqiong Wu

Institute of Tuberculosis Research
the 309th Hospital of Chinese PLA
China

Title: Immunogenicity and therapeutic effects of Ag85A/B chimeric DNA vaccine in mice infected with Mycobacterium tuberculosis
Biography:

Abstract:
The situation of tuberculosis (TB) is very severe in China. New therapeutic agents or regimens to treat TB are urgently needed.
In this study, Mycobacterium tuberculosis-infected mice were given immunotherapy intramuscularly with Ag85A/B chimeric DNA or saline, plasmid vector pVAX1, or Mycobacterium vaccae vaccine.
The mice treated with Ag85A/B chimeric DNA showed significantly higher numbers of T cells secreting interferon-gamma (IFN-γ) , more IFN-γ in splenocyte culture supernatant, more Th1 and Tc1 cells, and higher ratios of Th1/Th2 and Tc1/Tc2 cells in whole blood, indicating a predominant Th1 immune response to treatment. Infected mice treated with doses of 100 µg Ag85A/B chimeric DNA had an extended time until death of 50% of the animals that was markedly longer than the saline and vector control groups, and the death rate at 1 month after the last dose was lower than that in the other groups. Compared with the saline group, 100 µg Ag85A/B chimeric DNA and 100 µg Ag85A DNA reduced the pulmonary bacterial loads by 0.79 and 0.45 logs, and the liver bacterial loads by 0.52 and 0.50 logs, respectively. Pathological changes in the lungs were less, and the lesions were more limited.
These results show that Ag85A/B chimeric DNA was effective for the treatment of TB, signifantly increasing the cellular immune response, and inhibiting the growth of M. tuberculosis.






Isiaka Alade Owolabi

Tshwane University of Technology
South Africa

Title: Speciation of chromium in medicinal plants from selected farms in the vicinity of ferrochrome
Biography:
Owolabi IA currently writing his dissertation for awarding of MSc degree in Chemistry from Tshwane University of Technology, Pretoria, South Africa and working on the project titled Speciation of Chromium and Vanadium in Medicinal Plants from Selected Farms in the Vicinity of Ferrochrome and Vanadium mine. He is also working in the Chemistry department of the above mentioned institutions as Assistance Lecturer and Lab Assistance. It had acceptably presented in numbers of conferences and had two manuscripts waiting for the publication. He is will continually proceed for PhD.
Abstract:
Chromium (Cr) is one of the most and important trace metals which can be present in two oxidation states: toxic Cr(VI) and non-toxic (Cr III). Cr(III) is an important microelement for plant and animal nutrition and essentials for the maintenance of glucose as well as for the lipid and protein metabolism (Wang & Sañudo, 2009; Ng et al., 2013; Rigaud et al., 2013)). With regard to human health, Cr(III) is a required nutrient, with 50–200 g per day recommended for adults (Valko et al., 2005). On the contrary, Cr(VI) is toxic and carcinogenic, leading to lung cancer, skin allergy and probably also to asthma and renal diseases. A toxic effect for the biological systems is attributed to the ability of Cr(VI) to migrate across the cell membrane, thus enhancing the intracellular chromium concentration. Hexavalent chromium is rarely found in nature and is generally man-made, especially in fumes generated during the ferrochrome production. The permissible exposure limit (PEL) of chromium in air is 5 μg m-3 measured as Cr(VI). The dust with Cr(VI) could be a source of contamination of medicinal plants. Therefore, it is essential to monitor the concentration of Cr(VI) in the environment, to determine the risk of Cr(VI) to human health, not only from air breathing, but from the dust which settles on agricultural products grown in vicinity of chromium smelters and when into medicinal plants. For these studies, the samples of industrial dust, soil, bark of trees and medicinal plantssamples were collected in the vicinity of chromium smelters and from local market.All measurements were carried out using a Perkin Elmer atomic absorption spectrometer model AAnalyst 600 with Zeeman background correction.






Jose Manuel Lozano Moreno

Fundación Instituto de Inmunología de Colombia (FIDIC)
Colombia

Title: Structurally-modulated antigens as antimalarial vaccine components
Biography:
Jose Manuel Lozano has completed his Ph.D at the age in 2002 in the Universidad Nacional de Colombia, Bogota, Colombia and postdoctoral studies from Washington University School of Medicine and Le Laboratoire d’Immunologie et Chimie Thérapeutiques, Université Louis Pasteur, Strasbourg, France. He is the Head of the Biocatalysis Department at the Fundacion Instituto de Inmunologia de Colombia-FIDIC. He has published more than 50 papers in reputed journals and serving as an editorial board member of repute.
Abstract:
Obtaining new generations of anti-malarial vaccines have to consider systematic selection of non-polymorphic antigenic peptides from Plasmodium spp. Bearing in mind that such targeted-molecules shown low immunogenic capacity when tested as vaccine components, these have to be rationally modified to overcome such an immunological profile. Peptido-mimetics represent important tools for designing new structurally modulated immunogens. Site-directed substitution of specific peptide-bonds with given isostere peptide-bond surrogates, is opening alternative pathways toward novel antimalarial vaccine components. Thus peptide chemistry strategies for peptide modulation is providing to vaccinology important new elements to be taken into account when designing vaccines. On the other hand the rodent experimental model for immunological testing such modulated structural probes, is also providing new clues for including different Plasmodium antigens in new vaccine formulations as well as developing platforms for multiple antigen presentation have also to be considered for new vaccine candidate testing. This work presents data regarding advances in antimalarial synthetic vaccine compositions.






Javed N Agrewala

CSIR - Institute of Microbial Technology
India

Title: Self-adjuvanting promiscuous peptide of Mycobacterium tuberculosis augments polyfunctional Th17 cells and evokes better memory T cell response than BCG
Biography:
Dr. Agrewala did his PhD in 1986 from Agra University, Agra, India. In 1989 he joined as a faculty member at the CSIR-Institute of Microbial Technology, Chandigarh, India. He has done pioneer work in the field of Immunology of Infectious Diseases with particular interest in Vaccines. He is a recipient of the highest award in science in India “Shanti Swarup Bhatnagar Award” and a member of Indian Academy of Sciences. Dr. Agrewala has been a visiting scientist at the Hammersmith Hospital, London and Trudeau Institute, NY, USA. Dr. Agrewala has published 67 manuscript in the high impact journals.
Abstract:
Background: Vaccines have been successful in worldwide eradication of dreaded diseases like smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, such triumph has not been achieved in controlling tuberculosis (TB) globally. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered successful results in the Western population but has failed in TB-endemic areas. Hence, it is quite crucial to understand the immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. Consequently, introducing radical changes in the vaccines that would impart protection in the populations where BCG has failed. One of the main reasons considered for BCG failure in TB-endemic areas is impediment by environmental mycobacteria in its processing by antigen presenting cells and generation of memory T-cell response.
Methods: The peripheral blood mononuclear cells of sputum positive pulmonary TB patients and their house-hold contacts were separated by ficoll-hypaque gradient method. The cells were cultured with L91 and proliferation was monitored by CFSE-dye dilution assay and phenotypic markers by flowcytometry using fluorochrome tagged appropriate antibodies and their isotype-matched controls.
Results: Keeping in view the shortcomings of BCG, we developed a unique lipopeptide (L91) by linking the promiscuous peptide (sequence 91-110) of 16 kDa antigen of Mycobacterium tuberculosis to Toll-Like Receptor-2 agonist Pam2Cys. L91 does not require extensive antigen processing and targets and activate dendritic cells. This is evidenced by the fact that L91 significantly improved the activation and proliferation of polyfunctional Th1 and Th17 cells of the TB patients and their house-hold contacts. Furthermore, L91 surmounts the barrier of major histocompatibility complex polymorphism. Importantly, this peptide has self-adjuvanting property and induces enduring memory T cell response, which is significantly better than BCG.
Conclusion: L91 can be a potent future vaccine candidate against tuberculosis in TB-endemic and non-endemic zones.