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Wednesday, August 19, 2009
7:30am Morning Coffee (Breakfast Sponsored Presentation Opportunity Available)
8:25 Chairperson’s Remarks
Bilikallahalli Muralidhara, Ph.D., Principal Scientist, Pharmaceutical R&D, Global Biologics-World Wide Pharmaceutical Sciences, Pfizer Global Research & Development
8:30 Agonists of Pattern Recognition Receptors, including TLRs and NLRs, as Vaccine Adjuvants: Current Practice and Translational Development
Ofer Levy, M.D., Ph.D., Staff Physician & Principal Investigator, Infectious Diseases, Harvard Medical School/Children’s Hospital Boston
Molecular characterization of mechanisms by which human pattern recognition receptors (PRRs) detect endogenous danger signals and microbial infection has greatly expanded our understanding of the innate immune system. PRRs include Toll-like receptors (TLRs), nucleotide oligomerization domain-like receptors (NLRs), retinoic acid inducible gene-like receptors (RLRs) and C-type lectin receptors (CLRs). Research on the developmental expression of these systems in the fetus, newborn and infant is incomplete but has already yielded important insights into the susceptibility of newborns to infection. Progress in characterizing PRRs is thus informing and expanding the design of improved adjuvants. This review summarizes recent developments in the field of innate immunity with special emphasis on developmental expression in the fetus, newborn and infant and its implications for the design of more effective neonatal and infant vaccines.
9:00 Keynote Presentation:
Modulating the Release of Immunopotentiators to Enhance Potency of a Vaccine Formulation Using Anionic Microparticles Manmohan Singh, Ph.D., Director, Vaccines Research, Vaccine Delivery Group, Novartis Vaccines & Diagnostics, Inc.
Most new generation vaccine antigens, which are mainly comprised of purified recombinant proteins, will require the addition of an immunopotentiator to enhance potency. The way the immunopotentiator is delivered within a vaccine formulation can greatly effect its immunogenicity. Furthermore, formulating the immunopotentiator along with the antigen enables a more localized delivery at the site of injection and reduces potential for toxicity. We have developed novel formulations (emulsions and microparticles) that modulate the release of these immunopotentiators to enhance vaccine potency. The presentation will elaborate on some of these novel formulations and their in vivo evaluation in small animals with model vaccine antigens.
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9:30 Virosomes: An Approved Adjuvant/Carrier System for Next Generation VaccinesThomas Stauffer, Ph.D., Chief Executive Officer, Pevion Biotech
Virosomes are one of the few regulatory approved adjuvant/carrier systems and is used in three marketed products. This technology has outstanding characteristics concerning versatility and functionality. The predominantly synthetic carrier is very safe, applicable in a broad range of the population and shows reduced side effects over other adjuvants while still having an optimal immune stimulation capability.
10:00 Networking Coffee Break
10:30 W805EC, a Novel Nanoemulsion Adjuvant Elicits Robust Immune Responses to Commercial Influenza Vaccines Following Nasal Administration in Ferrets
Tarek Hamouda, M.D., Ph.D., Director, Vaccine Research, NanoBio Corporation
W805EC is an oil-in-water emulsion adjuvant composed of nanometer-sized droplets stabilized by surfactants. Different doses of commercial influenza vaccines (Fluzone® and Fluvirin®) were mixed with the W805EC and administered intranasally in ferrets. W805EC-adjuvanted commercial vaccines resulted in 50-fold reduction in antigen dose with over a 20-fold increase in hemagglutination inhibition geometrical mean titers when compared with intramuscular vaccination. Cross-protection to other H3N2 influenza strains not included in the vaccine was also impressive. The nanoemulsion vaccine resulted in protection of ferrets against challenge with live virus. W805EC has been intranasally administered in over 350 ferrets without any safety issues.
11:00 Novel Self-Adjuvanting Influenza Vaccines Delivered by Transcutaneous Patch
Alan R Shaw, Ph.D., President & Chief Executive Officer, VaxInnate
VaxInnate has developed a novel vaccine platform wherein an antigen of choice is coupled to a Toll-Like Receptor ligand, yielding a highly potent vaccine. We have applied this strategy to seasonal influenza, pandemic influenza and also to a conserved “universal” influenza antigen, the M2 ion channel ectodomain. In collaboration with the 3M corporation, we are developing a novel and convenient delivery system for these vaccines based on a transcutaneous patch. The combination of this new vaccine design and delivery vehicle may change the way we think about delivery of vaccines in both routine and emergency settings.
11:30 NKT Agonism as a Novel Immunization Strategy
Robert Burns, Ph.D., Chief Executive Officer, Immunox Therapeutics
NKT agonism represents an entirely novel approach to immunisation. It has the potential to address several of the major limitations of existing immunostimulatory strategies: it induces a response which mirrors Th1 effects, it avoids modulation by regulatory T cells, it agonizes myeloid derived suppressor cells and inhibits their immunosuppressive effects. It represents a pathway which acts in parallel to ‘classical’ TCR/peptide/MHC signalling and can synergize with this ‘classical’ pathway. Low molecular weight NKT agonists have been produced by chemical synthesis and their synergy with TLR agonism demonstrated. Additionally, NKT agonism has been used to develop potent immune responses to very poorly immunogenic targets and as such is expected to make a major contribution to improved effectiveness of vaccines against, for example, polysaccharide antigens, targets which have typically required complex chemical conjugation to haptens to induce immune responses.
12:00pm Sponsored Presentation (Opportunity Available)
12:15 Lunch on Your Own (Lunch Workshops Sponsorship Available)
1:40 Chairperson’s Remarks
Alan R Shaw, Ph.D., President & Chief Executive Officer, VaxInnate
1:45 Novel Approaches to Adjuvanting the Immune Potency of DNA Vaccines
Jean D. Boyer, Ph.D., Associate Professor, Pathology & Lab Medicine, and Director, Human Cellular Immunology Core, University of Pennsylvania
DNA vaccine technology has shown great promise in small animal models as a vaccine approach for infectious disease and cancer. However, significantly lower immune potency for this platform has been observed in larger animal models, non-human primates, and most importantly in humans. This major limitation has significantly impacted the growth of this important field. Recently, through combined approaches of genetic optimizations, novel formulations, improved delivery and unusual adjuvants, we have demonstrated dramatic advancement in the elicited immune potency in several critical model systems. These data will be discussed and their implications for vaccine development presented.
2:15 Enhancing the Potency of DNA Vaccines with Electroporation Delivery Technology
Claire Evans, Ph.D., Director, Therapeutic Programs, Ichor Medical Systems
Rationale and current status of DNA-based vaccines
Use of in vivo electroporation to enhance the delivery and potency
Enhancement in immunogenicity and protective efficacy in non-human primates and other animal models
Development of device technology to support translation of electroporation based DNA vaccine delivery into the clinical setting
Update on clinical studies underway for cancer and infectious disease indications
2:45 Formulation and Stability of DNA (Plasmid) Based Therapeutics
Bilikallahalli Muralidhara, Ph.D., Principal Scientist, Pharmaceutical R&D, Global Biologics-World Wide Pharmaceutical Sciences, Pfizer Global Research & Development
DNA and proteins have different physico-chemical natures, and so the art associated with formulating proteins cannot be directly translated to the formulation of DNA. Buffering species, temperature, pH and cations all uniquely affect the structure and stability of DNA. Delivery mechanism is another key consideration in DNA formulation development, especially in the formulation of plasmids for use as DNA vaccines. This talk will address the general challenges and approaches to nucleic acid formulation development, as currently practiced in industry and academia, focusing on the formulation of DNA vaccine candidates.
3:15 Networking Refreshment Break
3:30 DNA Vaccines for HIV-1
Dan Barouch, M.D., Ph.D., Associate Professor of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School
DNA vaccines for HIV offer substantial promise but have proven substantially less immunogenic than viral vectors. We will present data on the potential to improve the potency of DNA vaccines with adjuvants or with delivery technologies such as in vivo electroporation. We will also present data regarding alternations in the phenotype of cellular immune responses elicited by DNA vaccines and their potential relevance for protective efficacy.
4:00 DNA Vaccination for Prevention of Relapse in Myeloid Leukemia
Rose Ann Padua, Ph.D., Director, Research, Hematology, Inserm U940, Hôpital St-Louis
DNA vaccination as an adjuvant to boost responses to prevent progression of active disease in combination with an immunomodulator and inducer of apoptosis is an approach which we have shown to extend life-span in mouse models of acute promyelocytic leukemia (APL) and myelodysplasia (MDS). In the APL mouse model, we have shown the combination of all-trans retinoic acid (ATRA) + DNA vaccine rescues 50% of the mice from death. In a transgenic model of mutant NRAS and BCL-2 mediated MDS, we have shown a significant extension of lifespan of up to one year. We have developed tools for immunomonitoring to predict which mice will respond to treatment. Immunophenotyping of T-cell subsets and RQ-PCR of selected cytokines have been shown to correlate with outcome in these mouse models.
4:30 Progress Towards the Development of an Effective pDNA Prime, Live Vector Boost Vaccination Strategy for the Treatment and Prevention of Infectious Diseases and Cancer
Michael A. Egan, Ph.D, Director of Immunology, Profectus Biosciences
Over the last 15 years, numerous plasmid DNA and viral vector-based vaccine strategies have been developed and tested as candidate vaccines for the treatment and prevention of viral infections and cancers. In the case of HIV, very few of these vaccines have performed well enough to advance to large-scale clinical testing and none have proved to be efficacious. Recently, advances in several key enabling technologies (plasmid-based cytokine adjuvants, in vivo electroporation, development of live replication competent viral vectors) suggest that the successful development of an effective pDNA prime, live vector boost vaccination strategy for the treatment and prevention of HIV infection, and other infectious diseases and cancers, should be within our reach.