August 13-15, 2013
Novel Vaccines: Innovations & Adjuvants
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WEDNESDAY, August 14
8:00am Conference Registration & Morning Coffee
8:55 Chairperson's Remarks
Harriet Robinson, Ph.D., CSO, GeoVax Labs, Inc.
9:00 Featured Presentation
Adjuvants: Yesterday, Today and Tomorrow
Nathalie Garçon, Ph.D., Vice President and Head, Global Center for Adjuvants and Technology Innovation, GlaxoSmithKline Biologicals
Adjuvants have traditionally been used as vaccine constituents. However, their modes of action are only recently beginning to be unveiled, in particular by the discovery of Toll-like receptors (TLRs). TLRs mimic the immune defence triggers which are part of all infectious pathogens and lead to the activation of the immune system. Our understanding of how innate and adaptive immune responses interact in order to elicit an antigen-specific protective immune response following infection, as well as our understanding of the impact of adjuvants on the immune response to a given antigen, have enabled the development of new or improved vaccines for unmet medical needs. As of today, over a hundred adjuvants are being developed to enhance the specific immune responses to vaccines against various diseases. Although some of these adjuvants are part of approved vaccines, the majority of them are still being evaluated in preclinical or clinical trials. Notwithstanding the achievements to date, several setbacks are still being encountered such as the absence of an appropriate immune response, formulation or testing issues, and various theoretical concerns.
This presentation will review adjuvants of the past and their introduction into vaccines, the current adjuvant landscape, key events that helped their advancement and lessons learned, and will finish with the challenges lying ahead.
9:30 Making a "Super" Vaccine: Using TNF Superfamily Ligands to Adjuvant Antibody and T Cell Responses from HIV-1 DNA and Viral Vector Vaccines
Geoffrey Stone, Ph.D., Assistant Professor, Microbiology, and Group Leader, Immunology, HIV Immunotherapy Program, University of Miami Miller School of Medicine Biography
The TNF superfamily of ligands (TNFSFL) includes more than 15 inducers of dendritic cell and T cell costimulation. We present evidence that particular members of this family can be genetically engineered to increase DNA and viral vector vaccine immunogenicity and efficacy. Certain TNFSFL increase the quality of anti-gp120 antibodies, leading to enhanced neutralization and increased avidity in murine models. Other TNFSFL significantly enhance T cell responses, with distinct effects for DNA versus Ad5 vaccine formulations.
10:00 Inducing Broadly Cross-Protective Antiviral Immunity with Advax, a 3rd Generation Vaccine Adjuvant
Nikolai Petrovsky, Ph.D., Professor, Endocrinology Department, Flinders Medical Centre, Flinders University, and Research Director, Vaxine Pty Ltd. Biography
The move to highly purified antigens has created a problem of poor vaccine immunogenicity. Current thinking is this problem is best addressed by use of potent innate immune activators as adjuvants, thereby mimicking natural infection. However, using examples of vaccines against influenza, West Nile, and hepatitis B, data will be provided to show that bigger is not always better when it comes to adjuvant design.
10:30 Coffee Break with Exhibit and Poster Viewing
11:15 Improving the Efficacy of Cancer and Infectious Disease Vaccines with the Novel Synthetic Saponin Adjuvants
Jeffrey Gardner, CEO, Executive, Adjuvance Technologies, Inc.
Despite the liabilities QS-21 has remained the immunological adjuvant of choice and has proven its potency in many cancer, infectious disease and even degenerative disorder vaccine trials. Recently, all of these liabilities have been overcome by our semisynthetic approach to QS-21 synthesis. Our lead QS-21 analog (TiterQuil-1-0-5-5) and additional novel analogues have been selected through an exhaustive analysis of KLH conjugated vaccines against a series of glycolipid and peptide cancer antigens. Through the development of truncated synthetic and semi-synthetic QS21 analogues significant advances have been made that have overcome QS-21's issues resulting in improved purity, stability, safety, availability and adjuvant potency/toxicity ratio.
11:45 Development of Cyclic Dinucleotides (CDNs) as STING-Targeted Molecular Adjuvants
Thomas Dubensky, Ph.D., CSO, Research and Development, AduroBioTech, Inc. Biography
We demonstrate that vaccination with CDN-adjuvanted recombinant protein formulated to facilitate cytosolic trafficking induces antigen-specific CD4 and CD8 T cell responses, together with Th1-based antibodies which correlate with protective immunity in a viral challenge model. When co-formulated with an irradiated GM-CSF secreting tumor cell vaccine (STINGVAX) to mobilize and activate dendritic cells in vivo, CDNs promoted a significant reduction of tumor growth in a stringent B16 melanoma treatment model. STING represents a significant new adjuvant target for the development and clinical translation of effective vaccines for infectious and malignant diseases.
12:15pm Development of Protein Capsular Matrix Vaccine (PCMV) Platform Technology
Kevin P. Killeen, Ph.D., CSO, Matrivax Research & Development Corp.
Matrivax R&D Corp. is developing a proprietary vaccine platform technology, termed Protein Capsular Matrix Vaccine (PCMV), which entraps polysaccharides in a cross-linked CRM197 protein matrix. Matrivax is researching and developing pneumococcal and Typhoid PCMV candidates. Typhoid/pneumococcal preclinical data and typhoid PCMV GMP manufacture and Phase 1 trial plans will be discussed.
12:30 Luncheon Presentation (Opportunity Available) or Lunch on Your Own.
1:55 Chairperson's Remarks
Joe Cohen, Ph.D., Founder & Director, Cohen Biopharm Consulting
2:00 New Insight on the Induction of High Quality Antibody Responses by DNA Immunization
Shan Lu, M.D., Ph.D., Professor, Infectious Diseases and Immunology, University of Massachusetts Medical School Biography
While the DNA vaccination concept was formally accepted 20 years ago, human applications have been questioned due to its low immunogenicity as learned from early clinical studies. Recent results, including those from human clinical trials, indicate that DNA immunization is effective in priming B cells to elicit high quality antibody responses. Multiple previously unknown mechanisms in both innate and acquired immune systems are involved in this process.
2:30 Turning Self-Destructing Salmonella into a Universal DNA Vaccine Delivery Platform for Prevention and Treatment of a Diversity of Diseases
Wei Kong, Ph.D., Research Assistant Professor, Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University Biography
To turn a recombinant attenuated self-destructing Salmonella vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyper-invasive phenotype to maximize Salmonella host entry and host cell internalization, to enable Salmonella endosomal escape to release a DNA vaccine into the cytosol, and to decrease Salmonella-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases.
3:00 Novel HIV Vaccine Strategies
Dan H. Barouch, M.D., Ph.D., Associate Professor, Medicine, Chief, Division of Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center
This talk will review the current state of the HIV epidemic and the need for an HIV vaccine. Challenges, current approaches, and prospects will be discussed. Preclinical and clinical data will be reviewed.
3:30 Refreshment Break with Poster and Exhibit Viewing
4:15 A Microbial Achilles Heel: Poly-N-acetyl Glucosamine is a Ubiquitously Expressed Vaccine Target on Bacterial, Fungal and Protozoan Pathogens
Gerald Pier, Ph.D., Professor, Medicine, Microbiology and Immunobiology, Harvard Medical School Biography
Poly-N-acetyl glucosamine (PNAG), a β-1-6-linked polymer of N-acetyl glucosamine residues, is now known to be expressed as a surface polysaccharide by a large number of bacterial, fungal and protozoan parasites. As these capsule-like antigens form the basis for effective vaccines against S. pneumoniae, H. influenzae type b and meningococci, finding a conserved target in this vaccine-antigen category raises the possibility of inducing broadly-protective immunity to many pathogens ranging from streptococci to M. tuberculosis to C. albicans to malaria. Natural immunity to PNAG is common but ineffective due to a lack of deposition of complement opsonins onto microbial surfaces by natural human IgG2. Synthesis of a non-acetylated 9-glucosamine oligosaccharide (9GlcNH2) and conjugation to tetanus toxoid results in a vaccine that induces highly effective bactericidal/opsonic/protective antibody to the multitude of organisms expressing surface PNAG.
4:45 Breast Cancer Vaccines Targeting the Thomsen- Friedenreich Antigen
Kate Rittenhouse-Olson, Ph.D., Professor and Director, Biotechnology Program, Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo Biography
The Thomsen-Friedenreich Antigen (TF-Ag), (Galbeta1-3GalNacalphaO-Ser/Thr), is a tumor-associated carbohydrate antigen that is cryptic on normal cells but exposed and immunoreactive on tumor cells. It is expressed in more than 80% of human adenocarcinomas and plays a major role in tumor cell metastasis. Passive transfer of anti-TF-Ag antibody has been shown to block metastasis in both human and murine tumor models, and improve survival in tumor-bearing mice, indicating that active TF-Ag immunotherapy may be clinically effective. Creation of an immune response to this antigen has proven difficult, but 2 successful novel approaches of active immunization were made which will be described, one through utilization of gold nanoparticles (AuNPs) as a vaccine platform, and one through utilization of tanned red blood cells as a vaccine platform.
5:15 Single vs. Multiple Antigens
Graham J. Clarke, CEO & Director, ImmunoBiology, Ltd. Biography
Early vaccines contained multiple antigens from live, attenuated or sub-unit vaccines whereas many of the more recent vaccines deploy the approach of identifying a protective antigen (or limited number) plus targeting and adjuvanting mechanisms. Successful though this can be, it offers restricted protection where there is significant pathogen diversity. ImmBioVax technology has the potential to address both human and pathogen diversity, mimicking the innate impact on a pathogen ex vivo. The approach can be exemplified by ImmBio's development programmes against invasive meningococcal and pneumococcal diseases, as a well as TB.
5:45 Close of Day
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