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Cambridge Healthtech Institute’s Ninth Annual
Novel Vaccines
Part One: Adjuvants, TLRs & DNA Vaccines
August 11-12, 2014


Overview/Description: Speaker Biographies 

Vaccines are widely recognized as the single most important way to protect human health, yet problems of efficacy persist, baffling researchers. Adjuvanting vaccines has emerged as a promising approach to create more efficacious vaccines and reduce costs, yet safety issues continue to arise, and challenges for developing new adjuvants persist.

The Ninth annual “Novel Vaccines” meeting explores the breakthroughs in Adjuvant science including TLRs and new antigen combinations.  Adjuvant Safety and Mode of Action will be addressed along with a discussion focused on how to develop new adjuvants, and get them approved.  Toll-Like Receptors will also be discussed, as will DNA and RNA-Based vaccines. New approaches for developing vaccines against disease applications will be explored, along with a focus on Pertussis that highlights the recent spike in cases.


Recommended Dinner Short Course*

Vaccine Production & Manufacturing 


*Separate registration is required.


MONDAY, AUGUST 11

7:30 am Conference Registration & Morning Coffee


ADJUVANTS

8:35 Chairperson’s Opening Remarks

Nathalie GarçonNathalie Garçon, Ph.D., PharmD., Vice President, Head, Global Vaccine Centre for Adjuvants and Technology Innovation, GlaxoSmithKline

 

8:45 Opening Keynote Presentation:

The Regulatory Outlook for Future Vaccine Adjuvants

Norman BaylorNorman W. Baylor, Ph.D., President and CEO, Biologics Consulting Group, Inc.

There continues to be a need for the development of effective vaccines against emerging and neglected infectious diseases. Many vaccines under development against these diseases are recombinant molecules or subunits of pathogenic organisms. Many of these antigens do not elicit adequate immune responses, and require the incorporation of adjuvants. The development of safe and potent immunologic adjuvants and delivery systems that can enhance and direct vaccine-specific immunity is needed. In this presentation I will discuss the regulatory outlook and considerations for evaluating future vaccine adjuvants.


9:30 Vaccine Adjuvants: Where We Are Today and What Is Needed for the Future

Nathalie GarçonNathalie Garçon, Ph.D., PharmD., Vice President, Head, Global Vaccine Centre for Adjuvants and Technology Innovation, GlaxoSmithKline

 

10:00 Coffee Break

10:30 Novel Use of an NIR Laser to Adjuvant Vaccines

MarkCPoznaskyMark C. Poznansky, M.D., Ph.D., Associate Professor, Medicine, Harvard Medical School, and Director, Vaccine and Immunotherapy Center, Infectious Diseases Medicine, Massachusetts General Hospital

There is a critical unmet need for safe and efficacious vaccines. The team at the Vaccine and Immunotherapy Center (VIC) at MGH has discovered that a non-tissue damaging near infrared laser when delivered to an intradermal vaccination site can elicit a balanced, Th1 and Th2, immune response and increase the efficacy of a vaccine to influenza in a mouse lethal challenge model. We have begun to explore the mechanism of action of the laser in the skin. We will present published and preliminary data that supports the further exploration of this approach for human vaccination.

11:00 Development of an Adjuvanted Recombinant Subunit Vaccine against Dengue

Danilo CasimiroDanilo R. Casimiro, Ph.D., Executive Director, Vaccine Research, Merck & Co.

Preclinical studies of a recombinant subunit vaccine have been conducted in non-human primates to evaluate the immunogenicity and efficacy of tetravalent formulations. These preclinical studies have shown the capacity of the recombinant proteins to induce balanced tetravalent immune responses and protect against dengue virus infection. Data from these preclinical non-human primate studies will be presented along with results of a vaccine candidate being tested in a Phase 1 clinical trial in healthy, flavivirus-naïve, adults. An update on clinical trial status will also be provided.

11:30 Antiviral and Adjuvant Activities of RIG-I Agonists

John HiscottJohn Hiscott, Ph.D., Program Director, Vaccine & Gene Therapy Institute of Florida

RIG-I is a cytosolic sensor critically involved in the recognition of viral RNA and activation of the innate immune response to RNA virus infection. We evaluated the antiviral and adjuvant properties of small RNA-based RIG-I agonists on the replication of influenza virus, as well as two emerging arthropod-borne viral pathogens - dengue and chikungunya virus. An optimized 5’triphosphorylated RNA generated an antiviral response that inhibited multiplication of these viruses and served as an effective adjuvant in vivo in combination with H5N1 VLPs. Our studies highlight the therapeutic potential of RIG-I agonists as versatile antiviral agents.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own


RNA- & DNA-BASED VACCINES

1:55 Chairperson’s Remarks

Luis Brito, Ph.D., Head, Formulation Science, Novartis Vaccines & Diagnostics, Inc.

2:00 RNA: The New Revolution in Nucleic Acid Vaccines

LuisBritoLuis Brito, Ph.D., Head, Formulation Science, Novartis Vaccines & Diagnostics, Inc.

At Novartis, we have reinvented the gene vaccine by creating a synthetic self-amplifying mRNA vaccine platform. The Platform takes advantage of cell-free mRNA production from a transcription reaction and delivery with a synthetic delivery system. The broad utility of this novel vaccine technology has been demonstrated with genes encoding antigens from several pathogens and found to elicit broad and potent protective immune responses. Responses are comparable to a viral delivery technology, but without the inherent limitations of viral vectors.

2:30 Monitoring B Cell Development and Ig Gene Usage for Vaccine Development

Shan LuShan Lu, M.D., Ph.D., Professor, University of Massachusetts Medical School

Traditionally, serum antibody levels were the main measurements of general antibody responses to vaccination. Given the importance of B cell development in controlling the level and quality of antibody responses, it becomes increasingly significant to determine B cell responses in immunized hosts. Rapidly evolving technologies such as B cell ELISPOT and deep gene sequencing can provide useful information on the development and longevity of antigen-specific B cell responses as well as Ig gene usage from fresh or frozen PBMCs.

3:00 Synthetic DNA Vaccines for Difficult Targets

David WeinerDavid B. Weiner, Ph.D., Professor, Pathology and Laboratory Medicine, Chair, Gene Therapy and Vaccine Program, CAMB, University of Pennsylvania Perelman School of Medicine

Through multiple improvements including synthetic plasmid optimization, genetic adjuvant technology further combined with enhanced EP delivery, we now report a platform for vaccine/immune therapeutic development with major relevance to human disease settings. These combined DNA approaches drive immune responses similar or superior to live viral vector protocols in important model systems including HIV, HPV therapy, Influenza among others. We will present data that illuminate specific features of these synthetic DNA vaccines and benchmark their performance in animal models and in human studies.

3:30 Refreshment Break


INFLUENZA

4:00 Synthetic Influenza Vaccine Viruses

Philip DormitzerPhilip R. Dormitzer, M.D., Ph.D., Head of US Research, Global Head of Virology, and Vice President at Novartis Vaccines

Reliance on antiquated egg-based technology impairs influenza vaccine match to circulating strains and slows pandemic responses. H7N9 influenza emerged in China in March, 2013. Novartis and its partners at the J Craig Venter Institute used a new synthetic virus generation process to synthesize a H7N9 vaccine virus several days after it was posted by the Chinese CDC. Novartis produced clinical trial lots using the synthetic virus and mammalian cell culture technology, began trials in August, and initiated large-scale vaccine production.

4:30 Selected Poster Presentation
Novel Self Emulsifying Emulsion-Based Adjuvants for Enhancing Systemic Vaccine Potency
Ruchi Shah, Ph.D. Candidate, Northeastern University and Novartis Vaccines 

5:00 Development of a Second Generation Recombinant Influenza Vaccine Having Room Temperature Stability

Kathy Holtz, Ph.D., Formulation Development Scientist, Protein Sciences Corporation

Recombinant hemagglutinin (rHA) proteins are the active component in a newly approved influenza vaccine produced using the Baculovirus Expression Vector System (BEVS). Chemical changes occur during storage of the drug substance that affect tertiary, quaternary, and higher order structures of the rHA protein, and reduce the apparent potency. A strategy will be presented that addresses potency loss to reduce the cost of vaccine production, and confers room temperature stability to the drug substance thus offering the potential to bypass the cold chain for vaccine storage.

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day


TUESDAY, AUGUST 12

7:45 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee


PERTUSSIS

8:25 Chairperson’s Remarks

William EganWilliam M. Egan, Ph.D., Senior Expert, Novartis Vaccines & Diagnostics

 

8:30 Featured Presentation:

The Host Response to Pertussis Infection and Vaccination in the Baboon

Tod MerkelTod Merkel, Ph.D., Principle Investigator, Laboratory of Respiratory and Special Pathogens, Center for Biologics Evaluation and Research (CBER), FDA

Pertussis rates in the US have been steadily rising over the last thirty years despite nationwide vaccination coverage in children in excess of 95%. The US is now experiencing levels of pertussis not observed since the 1950s. We developed a baboon mode of pertussis to examine host responses to pertussis infection and vaccination with acellular and whole-cell pertussis vaccines. Our results identify key differences in vaccine and infection-induced immunity that suggest possible strategies for the development of next-generation pertussis vaccines.

9:00 Pertussis Resurgence – 2014: Facts, Fiction, Myths and Misconceptions

James CherryJames D. Cherry, M.D., M.Sc., Distinguished Research Professor, Pediatrics, David Geffen School of Medicine, UCLA, and Attending Physician, Pediatric Infectious Diseases, Mattel Children’s Hospital

The resurgence of reported pertussis in the US began in 1984. The magnitude of this resurgence dramatically increased during the last decade. The causes of this resurgence include: greater awareness, better diagnostic tests, less efficacious vaccines (DTP vs DTaP) and genetic changes in Bordetella pertussis. Today, however, the rate of pertussis is still ~20 fold less than in the prevaccine era and illness in vaccine failures is less severe than illness in nonvaccinated children.

9:30 Host Response to Bordetella Adenylate Cyclase Toxin: Should This Antigen Be Added to Acellular Pertussis Vaccines?

Erik HewlettErik L. Hewlett, M.D., Professor, Medicine and of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine

Adenylate cyclase toxin (ACT) is an essential virulence factor of Bordetella pertussis and a known protective antigen. It is not in acellular pertussis vaccines, however, because it was not available when these vaccines were developed. We are characterizing the host response to ACT and are mapping the epitopes to which convalescent sera react, in order to identify the appropriate domain/s of the toxin to use as an immunogen.

10:00 Coffee Break in the Exhibit Hall with Poster Viewing


TOLL-LIKE RECEPTORS

10:45 Systematic Analysis of Responses Induced by a TLR2 Ligand Immune Adjuvant

Lee WetzlerLee M. Wetzler, M.D., Associate Program Director for Research, Infectious Diseases, Professor, Medicine, and Associate Professor, Microbiology, Boston University School of Medicine

The Neisserial major outer membrane protein PorB, has significant immune activating activity, can act as a potent vaccine adjuvant and that the mechanism of this activity is mediated by its interaction with TLR2 and TLR1. New data shall be presented demonstrating its ability to enhance antigen uptake and antigen presenting cell migration. Finally we shall show that PorB induces specific genes and gene sets, highlighted by increased expression of cell cycle related genes and microRNAs, all associated with B cell proliferation and germinal center formation.

11:15 In vitro Modeling Identifies TLR8 Agonists that Are Effective Vaccine Adjuvants in vivo 

Ofer LevyOfer Levy, M.D., Ph.D., Senior Associate Physician in Medicine, Boston Children’s Hospital, and Professor, Pediatrics, Harvard Medical School
Vaccine adjuvants act via species-specific signaling mechanisms, yet biopharmaceutical development continues to employ rodent and other models that are not predictive of human responses. In this context, to enhance vaccine development, we have developed novel human in vitro models, including whole blood assays, dendritic cell arrays and microphysiologic tissue constructs that allow autonomous monocyte-derived dendritic cell development, to characterize species and age-specific responses to vaccine adjuvants. We have identified several Toll-like receptor-8 (TLR8) agonists as having unique immunostimulatory activity toward human newborn, infant and adult leukocytes and have now verified that such adjuvants dramatically increase antigen-specific antibody responses in vivo

This proof of concept suggests that our novel platforms are predictive of in vivo responses, thereby representing a disruptive innovation that may accelerate and de-risk vaccine development.

 

11:45 Sponsored Presentation (Opportunity Available)

12:00 pm Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

12:30 Close of Conference