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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/
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http://www.omicsgroup.com/vaccines-vaccination-conference-2014//abstract.php
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vaccines2014@omicsonline.net
vaccines2014@omicsgroup.co
vaccines2014@omicsgroup.biz

Day 1 : Sep-24-2014
Keynote Forum
09:35-10:00
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.\r\n\r\n
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?\r\n\r\nThe 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.\r\n\r\nThere 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

Michael G. Hanna

Chairman and Chief Executive Officer, Vaccinogen, Inc., USA

Keynote: The practical influence of tumor genomic heterogeneity on active specific immunotherapy
10:00-10:25
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

Nikolai Petrovsky

Flinders Medical Centre Research, Australia

Keynote: Vaccine Adjuvants; the good, the bad and the ugly
10:25-10:50
Biography:
Prof. Nikolai Petrovsky 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.
Group Photo
Coffee Break 11:00-11-15 @ Auditorium 3 Foyer






Vaccine adjuvants
Session Chair

Nikolai Petrovsky

Flinders Medical Centre Research, Australia




Session Introduction
11:15-11:35
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.






Magdalena Tary-Lehmann

Chief Scientific Officer, Cellular Technology Limited, USA

Title: Adjuvant-guidance of T cell responses
11:35-11:55
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.






11:55-12:15
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.






12:15-12:35
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.






12:35-12:55
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
12:55-13:15
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.
Lunch Break 13:15-14:00 @ Multi Purpose Hall 2






14:00-14:20
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.






Lakshmi Krishnan

National Research Council-Human Health Therapeutics, Canada

Title: Novel Lipid based Adjuvants and Delivery Systems for Induction of CD8 T cell immunity
14:20-14:40
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.






14:40-15:00
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.






15:00-15:20
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.
Coffee Break 15:20-15:35 @ Auditorium 3 Foyer






15:35-15:55
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.






15:55-16:15
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.






16:15-16:35
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.






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
16:35-16:55
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.






RandaHamadeh

Ministry of Public Health, Lebanon

Title: Polio outbreak in the Middle East –Update
16:55-17:15
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.






17:15-17:35
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
17:35-17:55
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.






Megha Kadam Bedekar

Central Institute of Fisheries Education, India

Title: Role of Interferon gamma as immune adjuvant in Labeorohita
17:55-18:15
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.
Panel Discussion 18:15-18:25






Biodefense vaccine
Session Chair

Leonard A. Smith

Scientific Director
U.S. Army Medical Research Institute of Infectious Diseases
USA




Session Introduction

Leonard A. Smith

Scientific Director, U.S. Army Medical Research Institute of Infectious Diseases, USA

Title: Finding a safe, efficacious and stable vaccine in the ricin protein fold
11:15-11:35
Biography:
Dr. Leonard A Smith received a B.A. degree in chemistry and zoology from the University of New Hampshire in 1972 and his Ph.D. degree in biochemistry from Georgetown University in 1978. He is the Senior Research Scientist (ST) for Medical Countermeasures Technology at USAMRMC and Scientific Director at USAMRIID. Dr. Smith has authored or co-authored more than 150 scientific publications, reviews and book chapters, and holds several patents for his work on bio-defense vaccine development. He has received numerous awards including the DOD Distinguished Civilian Service Award, the highest award given by the Secretary of Defense to career employees.
Abstract:
Ricin toxin, an extremely potent toxin produced from the bean of the ubiquitous Ricinus communis (castor bean plant), has been categorized by the US Centers for Disease Control and Prevention (CDC) as a category B biothreat agent that is moderately easy to disseminate. Ricin has the potential to be used as an agent of biological warfare and bioterrorism. A recombinant ricin toxin subunit A-chain (RTA) antigen was engineered to eliminate the toxin’s enzymatic activity and mitigate the undesirable aggregation and precipitation caused by exposure of hydrophobic surfaces on the RTA in the absence of its natural B-chain partner. An Alhydrogel-adjuvanted ricin A-chain 1-33/44-198 vaccine (RVEc™) was manufactured in compliance with cGMPs and evaluated for safety and efficacy during an open-label, uncontrolled Phase 1a escalating, multiple-dose clinical study. Healthy adults (10 per group) received a primary series of 20, 50 or 100 mcg of RVEc™ at 0, 28 and 56 days by IM administration of vaccine. Four subjects in the 50 mcg cohort group consented to a boost with 50 mcg RVEc™ ~20 months from their initial vaccination with subsequent plasmapheresis. Anti-ricin antibodies were purified from plasma and used for correlate of immunity studies in appropriate animal models. The vaccine was safe and well-tolerated at 20 and 50 mcg dose levels. At the 100 mcg dose, 2 subjects had elevated CPK levels after their first vaccination which resolved, but no further vaccinations at that dose were administered. The immune response elicited by the vaccine will be described during the presentation.






11:35-11:55
Biography:
Connie Schmaljohn is the U.S. Army Senior Research Scientist for Medical Defenses against Infectious Diseases. Her studies focus on the development of molecular vaccines for biodefense, and on the molecular biology of highly pathogenic viruses.
Abstract:
Hemorrhagic fever with renal syndrome (HFRS) is caused by infection with the hantaviruses Hantaan (HTNV), Seoul (SEOV), Puumala (PUUV), or Dobrava (DOBV) viruses. We developed candidate DNA vaccines for HFRS expressing the envelope glycoprotein genes of HTNV or PUUV and evaluated them in an open-label, single-center Phase 1 study. Three groups of nine subjects each were vaccinated on days 0, 28 and 56 with the DNA vaccines for HTNV, PUUV, or mixture of both vaccines using the Ichor Medical Systems intramuscular electroporation delivery device. Each vaccination consisted of 2.0 mg DNA in an injected volume of 1 mL saline. There were no study-related serious adverse events. Neutralizing antibody responses were detected in 5/9 and 7/9 individuals who completed all three vaccinations with the HTNV or PUUV DNA vaccines, respectively. In the combined vaccine group, 7/9 of the volunteers receiving all three vaccinations developed neutralizing antibodies to PUUV. The three strongest responders to the PUUV vaccine also had strong neutralizing antibody responses to HTNV. These results demonstrate that the HTNV and PUUV DNA vaccines delivered by electroporation separately or as a mixture are safe. In addition, both vaccines were immunogenic, although when mixed together, more subjects responded to the PUUV than to the HTNV DNA vaccine, suggesting immunological interference. Consequently, we have developed an optimized HTNV DNA vaccine that shows no interference in hamsters when mixed with the PUUV vaccine. Additional clinical testing of this new bivalent formulation is currently in progress.






11:55-12:15
Biography:
Dr. Arndtz-Wiedemann obtained her Medical Degree from the University of Munich in Germany. She has 18 years of experience in the pharmaceutical and biotech industry, particularly in the field of prophylactic vaccines and immunotherapeutic biologicals, working for companies like SmithKline Beecham, Berna Biotech and Bavarian Nordic. In her current position, Dr. Arndtz-Wiedemann is leading the Clinical Department at Bavarian Nordic, being responsible for the overall clinical strategy and the planning and execution of all clinical programs for development of the company’s preventive vaccines against infectious diseases.
Abstract:
Decades after its eradication, Variola virus still remains a threat due to its potential use in biological warfare and bioterrorism. Traditional replicating smallpox vaccines stockpiled for military use and post-outbreak mass vaccination are associated with rare, but potentially severe and even fatal adverse drug reactions. Moreover, their use is contraindicated in a considerable percentage of the population which is known to have an increased risk of serious adverse events, such as people with compromised immune systems and chronic skin conditions. MVA-BN® smallpox vaccine (IMVANEX® in Europe, IMVAMUNE® in the US and Canada), a live, highly attenuated vaccinia strain which does not replicate in human cells, is an alternative to traditional (replicating) smallpox vaccines. The safety database of MVA-BN® was recently enlarged to a total of more than 7,300 subjects due to ongoing phase II and III trials. Although these trials are still blinded, the safety data confirm the excellent safety profile of MVA-BN®, showing no relevant cardiac events, as well as none of the severe side effects associated with traditional smallpox vaccines due to their replicating nature. In the US, MVA-BN® obtained pre-Emergency Use Authorization (pre-EUA) for all populations with HIV and atopic dermatitis, which has led to stockpiling of 20 million doses of MVA-BN® for emergency use specifically in these populations. Recently, MVA-BN® has been granted marketing authorization in the European Union and in Canada. The acknowledged positive risk-benefit profile of MVA-BN® has opened up new opportunities for changing pre-event smallpox vaccination policies, but also for post-event preparedness plans such as stockpiling of MVA-BN®, including use for people with contraindications to traditional vaccines.






Michael Hust

Technische Universität Braunschweig, Institut für Biochemie, Biotechnologie und Bioinformati, Germany

Title: A vaccine pipeline: using phage display for identification of immunogenic proteins and generation of human antibodies for diagnostics and therapy
12:15-12:35
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.
Panel Discussion 12:35-12:45
Lunch Break 12:45-13:30 @ Multi Purpose Hall 2






Veterinary vaccines
Session Chair

Jean L Patterson

Texas Biomedical Research Institute, USA




Session Introduction
13:30-13:50
Biography:

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.






13:50-14:10
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
14:10-14:30
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.






14:30-14:50
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.






14:50-15:10
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.






15:10-15:30
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).
Coffee Break 15:30-15:45 @ Auditorium 3 Foyer






15:45-16:05
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.






16:05:16:25
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.






16:25-16:45
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.






16:45-17:05
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.
Panel Discussion 17:15-17:15