August 13-15, 2012
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TUESDAY, AUGUST 14
8:00am Morning Coffee
8:25 Chairperson’s Remarks
Antu Dey, Ph.D., Investigator II, Viral Vaccines, Novartis Vaccines & Diagnostics, Inc.
8:30 Development of Vaccines to Support Malaria Elimination
Ashley Birkett, Ph.D., Director, Pre-Clinical Research & Development, PATH Malaria Vaccine Initiative - Biography
Significant progress has been made in reducing mortality from malaria in recent years following the successful scale-up of multiple control measures. However, new interventions, including vaccines, are needed to sustain this progress and to support a transition from control to elimination and then eradication. Vaccines that induce immunity to block the transmission of parasites between humans and mosquitoes have the potential to contribute to driving levels of malaria transmission below the critical threshold at which it can be maintained in a community, resulting in local elimination of the parasite and the disease. Long term, a highly coordinated elimination effort would be designed to ‘shrink the map’ of malaria transmission toward an eventual goal of eradication. This presentation will focus on the current status of efforts to develop vaccines to support future elimination efforts, as well as highlighting some of the key challenges that will need to be overcome to achieve licensure of such a product.
» Keynote Presentation:
9:00 Malaria Vaccines: Many Purposes, Many Designs
Patrick Duffy, M.D., Chief, Laboratory of Malaria Immunology and Vaccinology, NIAID NIH - Biography
A recombinant protein vaccine called RTS,S reduces clinical malaria without preventing infection in interim results from a Phase 3 trial, and depends on adjuvant for efficacy. Future malaria vaccines aim to completely prevent infection, or to prevent severe disease, or even to prevent transmission to mosquitoes as part of planned elimination efforts. The different purposes for malaria vaccines may require a variety of designs and platforms. Immunity that prevents severe disease in children or pregnant women is naturally acquired, and therefore, anti-disease vaccines would be boosted during infection. However, naturally acquired immunity does not completely prevent infection or completely block transmission to mosquitoes. In animal models, vaccines that completely prevent infection require CD8+ T cells, and efforts are underway to establish platforms like heterologous prime boost for vaccines that elicit such responses. Some transmission-blocking vaccines target antigens expressed by the parasite only while it develops in the mosquito and therefore are not boosted by human infection; these vaccines will need to be designed to elicit high titer and durable antibody responses, and strategies such as protein-protein conjugates are being explored.
9:30 Development of Novel Antibody-Inducing Vaccines against Human Malaria
Simon Draper, Ph.D., Fellow, Jenner Institute, University of Oxford - Biography
The human malaria parasite Plasmodium falciparum continues to exert a huge burden on global public health, whilst the development of a highly efficacious vaccine has proved extremely challenging. The disease-causing blood-stage and the transmitting mosquito-stage of the parasite’s life-cycle are both known to be susceptible to antibodies. However, the field has faced significant hurdles in translating this knowledge into efficacious clinical subunit vaccine products. This talk will focus on the development of new approaches to vaccine antigen identification and delivery in the context of human malaria, and will summarize experience to date of these new strategies in Phase I/IIa clinical trials.
10:00 Coffee Break with Poster and Exhibit Viewing
10:45 Creation of a Liver Stage Plasmodium Falciparum 3D7 Liver Stage Antigen Library for T Cell Antigen Discovery
LeeAnn Blalock, Ph.D., Scientist, Malaria, Genocea Biosciences - Biography
Generation of an effective malaria vaccine has been hindered by the availability of antigens that elicit a protective CD8+ T cell response in an unbiased way. To address this problem, an expression library from P. falciparum 3D7 has been generated composed of 901 full length liver stage genes selected to be expressed during the sporozoite stage of development based on transcriptome analysis. Using ATLAS™, a novel technology that facilitates intracellular processing of full length protein and presentation by human donor antigen presenting cells, these full-length proteins are currently being used to screen CD8+ and/or CD4+ T cells from human blood donors who have been exposed to P. falciparum. Results from these screens will identify T cell antigens that may lead to the development of a protective subunit vaccine for the prevention of malaria.
11:15 HIV Mosaic Vaccines: An Antigen Design Strategy to Contend with Highly Variable Pathogens
Bette Korber, Ph.D., Laboratory Fellow, Los Alamos National Laboratory - Biography
This talk will describe a strategy for vaccine design in the context of a highly variable pathogen. HIV evolves rapidly, and mutations that have repeatedly arisen in the circulating population are likely to reflect common patterns of immune evasion during natural infections, selected to escape the assault by the human immune response while retaining fitness. An effective vaccine response should be able to block HIV infection by most of the circulating forms of the virus. The goal of our mosaic vaccine design is to maximize the cross-reactive potential of vaccine elicited immune responses. Our T cell mosaic design is currently moving into Phase I clinical trials, and people have begun to apply the strategy to other variable pathogens.
11:45 Quantitative Analysis of Influenza Hemagglutinin Binding
Peter Coombs, Ph.D., Postdoctoral Fellow, MRC National Institute for Medical ResearchInfluenza virus hemagglutinin (HA) mediates receptor binding and membrane fusion in influenza infections. The receptors to which HA binds are sialic acids, which are found on cell surface glycoproteins and glycolipids. We have developed a quantitative assay to measure the binding of influenza viruses to immobilized sialic acids using the Octet RED instrument from Fortebio. We are able to measure virus binding in real time and determine the affinity, and therefore specificity, for human- and avian-preferred sialic acid receptors. The close proximity on HA of the sialic acid binding pocket and binding sites for antibodies that neutralize infectivity is consistent with observations that mutations that prevent antibody binding can also result in changes in the affinity or specificity of receptor binding and vice versa. This talk will also show work performed on the Octet RED examining quantitative antibody binding to influenza viruses and antibody cross-reactivity.
12:15pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:40 Chairperson’s Remarks
Heidi Drummer, Ph.D., Lab Head, Viral Fusion Laboratory, Burnet Institute
1:45 HIV-Specific ADCC: A Novel Vaccine Modality
Ivan Stratov, M.D., Ph.D., Senior Research Fellow, Microbiology and Immunology, University of Melbourne - Biography
The partial success of the RV144 HIV vaccine trial has energized researchers in their quest for an effective and safe HIV vaccine. Attention has focused on non-neutralizing Abs (such ADCC-mediating Antibodies), which were induced significantly more in vaccines than control subjects. We have developed a technique for indentifying and purifying ADCC-mediating antibodies and have shown that such antibodies significantly target non-envelope epitopes, force viral escape and can reduce HIV replication in vitro. These data form the basis for a novel vaccine strategy against HIV.
2:15 Overactivation of Innate Immune Responses Cripples Adaptive T-Cell Responses: Implications for HIV Vaccine Development
Adriano Boasso, Ph.D., Wellcome Trust Research Fellow, Department of Medicine, Imperial College, London; Division of Infectious Diseases, Immunology Section, Chelsea and Westminster Hospital - Biography
Plasmacytoid dendritic cells (pDCs) play a critical role in balancing immunostimulatory and immunosuppressive signals during anti-viral innate immune responses, and regulate the strength and efficacy of the adaptive T-cell response. Overactivation of pDCs by the human immunodeficiency virus (HIV) is thought to promote the pathogenesis of AIDS. We generated HIV particles with reduced ability to activate pDCs, and demonstrated their ability to induce more potent memory T cell responses. Fine modulation of pDC activity is critical in determining the outcome of prophylactic and immunotherapeutic vaccination.
2:45 Rationale Selection and Evaluation of Two HIV‑1 Subtype C Gp120 Antigens as Protein Boosts for Proof-of-Concept Phase I/II Clinical Trial in the Republic of South Africa
Antu Dey, Ph.D., Investigator II, Viral Vaccines, Novartis Vaccines & Diagnostics, Inc. - Biography
Due to the enormous diversity of HIV-1 strains and the lack of a clear correlate of immune protection against HIV, it has been challenging to identify what in vitro properties in Env might translate into the elicitation of protective response(s) in vivo. The partial efficacy and recent assessment of correlates of risk from the RV144 Phase III trial has energized the HIV vaccine field and led to new hypotheses that may guide future Env antigen selection as well as vaccine regimen. Here, the selection of two HIV‑1 Subtype C gp120 antigens are described based on (i) antigenicity as measured by ligand binding, (ii) protein productivity and homogeneity as measured by high monomer content, and (iii) immunogenicity studies in multiple animal species as measured by virus neutralization and epitope mapping.
3:15 Refreshment Break with Poster and Exhibit Viewing
4:00 Innovation in TB Vaccine Development
Michael J. Brennan, Ph.D., Senior Advisor, Scientific & Global Affairs, Aeras Global TB Vaccine Foundation
TB vaccine development has the huge challenge of having no surrogate of protection, poorly validated animal models, and the need to conduct huge efficacy trials. Given this background, innovative methods are being used to gate different vaccine platforms and candidates. We will discuss the use of novel human and animal challenge models, systems immunology, an iterative surrogate analysis of clinical trial samples in TB vaccine development.
4:30 Vaccines against Tuberculosis: New Strategies for an Old Disease
Philana Lin, M.D., Assistant Professor, Department of Pediatrics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Children’s Hospital of Pittsburgh of UPMC - Biography
Dr. Lin will discuss the contribution of the non-human primate models in testing vaccines against tuberculosis. She will also present novel methods of measuring vaccine outcomes.
5:00 Modulation of Protection against Mycobacterium Tuberculosis by Different Adjuvanted Vaccines
Rhea N. Coler, Ph.D., Vice President, Pre-Clinical Biology, Infectious Disease Research Institute (IDRI) - Biography
An effective protein-based vaccine for tuberculosis (TB) will require a safe and effective adjuvant that can influence and direct the immune response to enable a desired outcome. A T helper 1 (Th1) response, including antigen-specific production of interferon-gamma (IFN-g), is needed to provide protection against Mycobacterium tuberculosis infection. In this study we combine our lead candidate TB vaccine, ID93, with a synthetic TLR-4 agonist, glucopyranosyl lipid adjuvant (GLA) mixed with an o/w emulsion. The results demonstrate the importance of modulating protection against TB by properly formulating subunit vaccines with effective adjuvants.
5:30 Close of Day
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