Cambridge Healthtech Institute’s Ninth Annual
Part Two: Emerging Vaccine Technologies
August 12-13, 2014
Overview/Description: Speaker Biographies
An ever-expanding array of technologies and approaches are being employed to create more efficacious vaccines and advance the field, including developing predictive models and Synthetic Biology. Next- Generation Sequencing (NGS) is also being used to elucidate viral evolution in an effort to more deeply understand infection.
The Ninth annual “Novel Vaccines” meeting tackles these emerging technologies in an effort to crystallize where the field is headed, along with novel modes and routes of delivery, such as patches, VLPs and microparticles. Ways to test vaccines in order to ensure quality will also be explored, including rapid microbiological methods (RMM), potency tests, and large-scale arrays. Vaccine stability and targeting specific populations will also be discussed as part of the push to achieve more effective vaccines and support vaccine development.
TUESDAY, AUGUST 12
12:30 Conference Registration
1:55pm Chairperson’s Opening Remarks
2:00 Keynote Presentation:
Synthetic Genomics to Address Emerging Threats and Global Supply Challenges
Bolyn Hubby, Ph.D., Senior Director, Head, Vaccine and Phage R&D, Synthetic Genomics Vaccines, Inc.
The potential of synthetic biology is being realized in the vaccine space. This presentation will describe the application of synthetic genomics tools, coupled with automation, to produce synthetic vaccine candidates across a variety of targets. SGVI and partners have applied this technology to improve response to emerging threats and the lead influenza program has advanced through initial clinical testing. Converting digital sequence information into DNA, RNA, and protein in an automated fashion enables distributed manufacturing to address vaccine supply challenges.
2:45 Databases and in silico Tools for Vaccine Design
Yongqun (Oliver) He, D.V.M., Ph.D., Associate Professor, Microbiology and Immunology, Affiliated Member, Center for Computational Medicine and Biology (CCMB), Member, Comprehensive Cancer Center, University of Michigan
Many databases and tools are available to support rational vaccine design. The Protegen protective antigen database, VirmugenDB “virmugen” database, and Vaxign vaccine design tool are parts of the integrative VIOLIN vaccine database and analysis system (http://www.violinet.org). The analyses of Protegen and Virmugen data allow prediction of genes for subunit and live attenuated vaccine development. Vaxign is the first Web-based vaccine design program based on reverse vaccinology. New vaccine design methods are being developed based on the community-based Vaccine Ontology (VO).
3:15 Sponsored Presentation (Opportunity Available)
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Engineering Cancer Immunotherapy One (DNA) Sequence at a Time
Mark Bagarazzi, M.D., CMO, Inovio Pharmaceuticals
Inovio is developing cancer immunotherapeutics by targeting both viral oncogenes (HPV E6, E7) as well as self proteins associated with cancer progression and metastases (PSA, PSMA, hTERT). Our common approach involves enhancing the delivery of optimized DNA sequences with the use of our proprietary in vivo electroporation system. We will share both preclinical and clinical data regarding several cancer indications.
4:45 Deep Profiling of HIV-Specific T Cell Responses by Mass Cytometry
Damien Soghoian, Ph.D., Researcher, Virology, Harvard University
HIV-specific T cell responses play an important role in the antiviral immune response and will likely be critical for an HIV vaccine. However, the functional and phenotypic features of these cells that are most beneficial remain unclear. Mass cytometry, or cytometry by time of flight (CyTOF), affords the ability to obtain an unprecedented level of information on single cells. This presentation will describe the highly multiparametic profiling of HIV-specific T cells by CyTOF and how insights gained from this analysis may inform HIV vaccine development.
5:15 Robust Induction of Cytotoxic T Lymphocyte (CTL) Response through Low-Frequency Sonophoresis Assisted Transcutaneous Immunization
Diviya Sinha, Ph.D., Technical Instructor, Biology, Massachusetts Institute of Technology (MIT)
Traditional vaccinations have had limitations at inducing a potent CTL response; essential for protection against intra-cellular infections and effective cancer vaccine development. Here, we demonstrate that a needle-less skin vaccination strategy based on low-frequency sonophoresis (LFS) is able to induce long-lived antigen specific CTLs in the absence of any external adjuvants. Innate adjuvancy associated with LFS skin pretreatment is hypothesized to result in the observed induction of CTLs, which respond rapidly against a viral LCMV challenge months following a single immunization.
5:45 End of Day
WEDNESDAY, AUGUST 13
7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:25 Chairperson’s Opening Remarks
8:30 Genomic Analysis of Vaccine Response in Humans
W. Nicholas Haining, B.M., B.Ch., Assistant Professor of Pediatrics, Harvard Medical School, and Scientific Co-Leader, HSCT Program, Pediatric Oncology, Dana-Farber Cancer Institute Children’s Hospital, and Associate Member, Broad Institute of Harvard and MIT
Vaccination is one of the most effective methods of preventing human disease. However, many vaccines are not universally protective and even widely used vaccines fail to achieve protective immunity. This presentation will discuss advances in genomic approaches to identify the biological features of the early vaccine response that predict the subsequent development of vaccine immunity.
9:00 Identification of Novel Vaccine Candidates Using a Robust Immunogen Optimization System
Sean Du, Ph.D., COO, Altravax, Inc.
Altravax has developed a robust Immunogen Optimization System™ (IOS) that can be applied to a variety of vaccine candidates for the improvement of overall immunogenicity, antibody cross-reactivity, potent T-cell responses, manufacturing efficiency, and product stability. Using IOS, we have developed a preclinical vaccine pipeline including a novel preventive dengue vaccine, based on a single-component VLP that can induce tetravalent immunity capable of neutralizing all four dengue serotypes, and a first-in-class therapeutic vaccine for chronic hepatitis B infection.
9:30 Innovative Preclinical Models for Developing Staphylococcus aureus Vaccines
Fabio Bagnoli, Ph.D., Project Leader, Novartis Vaccines and Diagnostics
Staphylococcus aureus is a major human pathogen and current antibiotics are not efficacious against emerging multidrug resistant strains. Unfortunately, S. aureus vaccine development is hindered by the lack of known correlates of protection. Three-dimensional organotypic human tissue models may represent a valid alternative to animal infection models. This talk will present data on a novel S. aureus vaccine formulation as well as research to develop innovative preclinical models for predicting vaccine efficacy in humans.
10:00 Sponsored Presentation (Opportunity Available)
10:15 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Genomics of TB and HIV Disease Progression in African Children
Graeme Mardon, Ph.D., Professor, Developmental Biology & Pathology, Baylor College of Medicine
The Collaborative African Genomics Network (CAfGEN) seeks to integrate genetic and genomics technologies to identify host factors that are important to the progression of HIV and HIV-TB infection in sub-Saharan African children. This will include recruitment of cohorts of HIV and HIV-TB infected children, whole-exome and RNA sequencing, and SNP genotyping of patients at the extremes of HIV and TB disease progression. These projects will provide important mechanistic insights to pediatric HIV and HIV-TB disease progression.
11:30 T Cell Crossreactivity, Heterologous Immunity, and Viruses
Liisa K. Selin, M.D., Ph.D., Professor, Pathology, University of Massachusetts Medical School
Heterologous immunity occurring as a consequence of T cell crossreactivity between unrelated pathogens has been shown by us with animal models to contribute to reduced (beneficial) or enhanced viral loads, and remarkably altered immunopathology (detrimental). Our objective is to determine how crossreactive T cells impact T cell selection and function, and influence disease outcome as the host is exposed to subsequent acute or persistent infections. Insights on these issues are necessary for the intelligent design of effective modern vaccines without unwanted side effects.
12:00 pm Development of a Robust, Defined Animal-Free Virus Production Medium Optimized for Microcarrier Culture
Mark Szczypka, Ph.D., Pall Corporation
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:55 Chairperson’s Remarks
2:00 Nanosponge Toxoid for Safe and Effective Vaccination
Liangfang Zhang, Ph.D., Associate Professor, Nanoengineering and Moores Cancer Center, University of California, San Diego
Toxoid vaccines are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. A novel toxin-detainment strategy is disclosed that employs a unique toxin nanosponge to arrest and deliver non-disrupted pore-forming toxins for immune processing. Mice vaccinated with the resulting nanosponge toxoid show superior toxin-specific humoral response and protective immunity against both systemic and subcutaneous toxin challenges. These results indicate that the immunogenicity and efficacy of toxoid vaccines can be enhanced by the non-disruptive detoxification approach.
2:30 Development of a Dendritic Cell Receptor-Targeted Multi-Antigen HIV Vaccine that Generates both Cellular and Humoral Immune Responses Without Adjuvant
Rajan George, Ph.D., President & CSO, Akshaya Bio, Inc.
A Chimigen® HIV Vaccine that incorporates six engineered HIV antigens: Gag, Env, Tat, Rev, Vpr, and Vpu and Fc fragment which generates multi-antigen, multi-epitopic humoral and cellular immune responses in the absence of any added adjuvant has been produced and evaluated. The vaccine has both prophylactic/early intervention therapeutic applications.
3:00 An Ultra-Low Dose Live-Attenuated Influenza Vaccine – An Opportunity to Overcome Current Manufacturing Bottlenecks
J. Robert Coleman, Ph.D., MBA, Co-Founder, Executive Vice President, Vaccine Development, Codagenix, Inc.
Using our SAVE vaccine platform, we have developed a clinically relevant H1N1 live-attenuated Influenza vaccine strain against the 2009 pandemic virus that is highly immunogenic in ferrets. The vaccine has efficacy at ultra-low doses, doses 1,000-FOLD lower than current vaccines. Due to its low dose requirement, our vaccine technology could overcome critical bottlenecks in the influenza vaccine manufacturing process as well as provide a seasonal vaccine that is antigenically identical in all segments to the target strains with high efficacy.
3:30 Refreshment Break
3:45 Interbilayer-Crosslinked Multilamellar Vesicles: A System for Co-Delivery of Antigen and Adjuvant
Adrienne V. Li, Ph.D., Senior Scientist, Vedantra Pharmaceuticals, Inc.
Vedantra Pharmaceuticals has been developing a ‘toughened’ liposome for enhancing vaccine delivery. Our technology, Interbilayer-Crosslinked Multilamellar Vesicles (ICMVs), is formed by crosslinking of adjacent lipid bilayers within a liposome. ICMVs show enhanced protein antigen loading and extended drug release kinetics allowing efficient vaccine delivery. When the malaria antigen VMP001 is loaded into ICMVs, immunized animals generated higher titer, higher avidity, and more durable antibody response with broader epitope recognition by immune sera, compared to animals that received the soluble VMP001 protein.
4:15 Tuning the Direction and Magnitude of the Immune Response with New Nanomaterial-Based Vaccines
Tarek Fahmy, Ph.D., Associate Professor, Biomedical Engineering, Engineering & Applied Science, Yale University
Vaccine development has progressed significantly since Jenner and Pasteur, moving from whole microorganisms towards subunit vaccines containing only their antigenic proteins. Nanoparticulate-based vaccines have tunable physical properties, allowing for encapsulation and controlled delivery of multivalent antigen, immunostimulatory factors and incorporation of pathogen associated molecular patterns (PAMPs) targeting dendritic cells. Overall, immune responses can both quantitatively and qualitatively, be tuned efficiently using such systems. Here we discuss advances in both immunology and nanomaterials that have brought particulate-based vaccines to clinical applications.
4:45 Exploring the Role of Size and Shape Impact on Immune Response through PRINT Technology
Michele Stone, Ph.D., PMP, Director, Vaccines, Liquidia Technologies
Particle technology is becoming increasingly prominent as a vaccine delivery system. PRINT technology allows for independent manipulation of particle, size, shape, charge, hydrophobicity, and composition. A variety of particles ranging from 80 to 10,000 nm were produced to explore controlled delivery of antigens and immunostimulants. Using a broad range of matrix materials formulated with active antigens and adjuvants, PRINT technology has defined specific sizes and shapes that appear to have superior effects on B cell and T cell immune responses.
5:15 Close of Conference