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Day 1 | Day 2 | Speaker Bios
7:00am Morning Coffee (Breakfast Sponsored Presentation Opportunity Available)
8:25 Chairperson’s Remarks
Jamie Scott, Ph.D., Professor, Molecular Biology & Biochemistry, Simon Fraser University
8:30 Novel Strategies for Synthetic Vaccines by Mimicry of Discontinuous Epitopes and Multivalency
Rob M.J. Liskamp, Ph.D., Medicinal Chemistry and Chemical Biology, Utrecht University
Proper alignment of mimics of the native shape of a protein or its fragments, which is often needed to induce protective antibodies, is beneficial for development of fully synthetic vaccines. We have applied synthetic scaffolds in order to mimic structurally defined epitopes by confined presentation of several different peptide arms. In addition, dendrimers are employed in multivalency approaches. Using the Bordetella pertussis protein pertactin as a model, we have shown that protective antibodies can be obtained directed towards a discontinuous epitope. However, the structural ability of linear peptides to achieve an adequate mimicry of the structure of a protein is limited. Therefore, we have developed efficient approaches for the preparation of peptide-loops, which provide better mimics of the native shape of a protein having loops, turns, etc. Moreover, the exploration of efficient and convenient approaches is pursued for attachment of these peptide-loops to synthetic scaffolds as well as to dendrimers and polymers for multivalency. These approaches may open up new avenues towards mimicry of protein surfaces and protein discontinuous epitopes towards fully synthetic vaccines. Biography
9:00 Filamentous Phage as a Carrier for Conjugate Vaccines
Jamie Scott, Ph.D., Professor, Molecular Biology & Biochemistry, Simon Fraser University
The surface of the filamentous bacteriophage comprises ~2600 primary amine-reactive sites for conjugation spaced ~37 angstroms apart. As such, phage can be used as highly immunogenic carriers for peptides and haptens that have been chemically conjugated to its surface. We have engineered the phage to remove immunodominant epitopes on its surface, so as to enhance the antibody response against weakly immunogenic peptides or carbohydrates. This approach succeeded in improving the antibody response against a peptide, and we are currently attaching short carbohydrate chains to the phage coat to mimic the “glycan shield” of the HIV-1 envelope, with the goal of eliciting HIV-1-neutralizing antibodies. I will report our progress in this project, along with an investigation of the anti-phage B-cell response that should provide a means for controlling and improving antibody response against targeted molecules. Biography
9:30 “Universal” Influenza Vaccine: Progress and Challenges
Hersh Mehta, Ph.D., Head, Product Conception and Development, sanofi pasteur Biologics
Unlike current vaccines that are based on hemagglutinin (HA) protein, which varies structurally between different type A influenza strains and also seasonally within subtypes, vaccine development based on conserved M protein has recently gained considerable interest. If successful, this approach can address challenges associated with seasonal influenza vaccines and/or pandemic preparedness. We have used a region of M protein that is significantly conserved between type A influenza viruses, genetically fused with carrier protein, and expressed the chimeric protein in E.coli. The product self assembles into well defined structures of 30nm virus-like particles that are composed of protein and RNA. Accelerated stability studies provided understanding of probable mechanism of degradation for improving formulation during life cycle management. Following acceptable toxicological studies, clinical trial in humans showed safe and immunogenic responses. Challenges in product development will be discussed. Biography
10:00 Networking Coffee Break with Exhibit and Poster Viewing
10:45 On the Path to the Clinic: Rapid Discovery of Protective T Cell Antigenic Targets from Naturally Infected Humans
Mojca Skoberne, Ph.D., Head, Cellular Immunology, Genocea Biosciences
Genocea Biosciences is developing novel T cell-stimulating vaccines against multiple pathogens that have high unmet medical needs. The company’s proprietary high-throughput T cell antigen discovery technology allows for selective identification of antigens that have a high potential for success as protective vaccines. The identified antigens can be immediately incorporated into existing antigen delivery systems to produce multivalent vaccine formulations that result in the in vivo stimulation of protective CD8+ and CD4+ T-cells. Genocea is currently developing vaccines for Chlamydia trachomatis, Streptococcus pneumoniae, Herpes Simplex Virus Type-2, and other undisclosed targets. Biography
11:15 Development of a New Generation of Adenovirus (Ad5) Vaccines
Raj Dua, Ph.D., VP, Operations, Product Development, Etubics Corporation
Adenovirus (Ad) is a family of DNA viruses characterized by an icosohedral, non-enveloped capsid containing a linear double-stranded genome. Current generation of Ad5 [E1-] deleted vector vaccine has shown great promise as an immunotherapeutic agent in a variety of oncological and infectious diseases. One of the major challenges facing Ad5 based vector use is the presence of pre-existing immunity to Ad5 in humans, and this immunity may preclude the use of current generation Ad5 [E1-] vaccines. Etubics has developed a new generation of Ad5 vaccines with additional deletion in the E2b region. Etubics’s novel Ad5 [E1-, E2b-] platform can overcome the presence of pre-existing Ad5 immunity and can deliver multiple doses of the immunotherapeutic agent to the same vaccine. We have successfully developed an Ad5 [E1-, E2b-] against Carcinoembryonic Antigen (CEA) to treat colon cancer patient. I will present pre-clinical, process development, manufacturing and early clinical data on the use of Ad5 [E1-, E2b-]-CEA vaccine. Biography
11:45 Novel Platform for Low Cost, Orally Administered Vaccines: Replication Competent Adenovirus Vectored Vaccines Produced In A549 Human Lung Cells
Deborah A. Mosca, Ph.D., Vice President, Project Management, PaxVax Inc.
PaxVax has developed a proprietary replicating vaccine vector technology that can express protein antigens from bacteria, viruses, or parasites. To date, using these methods, more than 80 Adenovirus serotypes 4 and 7 vectored products have been designed, produced and tested for functional expression of the transgene products and/or immunogenicity. These include recombinant Ad4 vectors encoding hemagglutinin from multiple strains of influenza (e.g. H5N1, H1N1, and seasonal variants), protective antigen from anthrax, and envelope proteins from HIV.
In order to achieve low cost productivity for our novel Ad4 vectored vaccines, we compared replication of our vectors in a number of cell substrates derived from various human organs such as lung (MRC-5, A549, H1299), colon (CaCo2, SW480), duodenum (HuTu 80), liver (HepG2), and cervix (HeLa). The results demonstrated that A549 was far superior for production of Ad 4 than other cell substrates. In addition, A549 meets the criteria for an optimal cell substrate such as tropism for the cell, productivity per infected cell, cell density, and the ability to adapt to serum free and suspension culture. PaxVax has prepared a Master Cell Bank (MCB) of adherent A549 cells and is in the process of completing release tests in concordance with the FDA guidance. Vials from a Working Cell Bank (WCB) will be made available to others interested in evaluating the suitability of A549 for other applications.
The potential advantages of PaxVax orally administered, replicating Ad4 vector vaccines compared to traditional injectable vaccines for recipients include convenience, ease of administration, lower dosage and potential for enhanced immunogenicity with a replicating vector, and lower delivery costs. The advantages of such vaccines for society at large include faster manufacturing, ease of stockpiling and more rapid distribution to the needy.
12:15pm End of “Novel Vaccines: Design & Development” meeting
Day 1 | Day 2 | Speaker Bios