Friday, August 15
Production: Heading to the Clinic & to the Patient
7:30am Registration and Morning Coffee
INTO THE CLINIC
8:00 Chairperson’s Remarks
Trevor Castor, Ph.D., CEO, Aphios Corporation
KEYNOTE PRESENTATION
 8:05 Getting your Biologic Product to the Clinic – Points to Consider
Nicholas I. Obiri, Ph.D., Senior Regulatory Affairs Specialist, Office of Regulatory Affairs, National Institute of Allergy and Infectious Diseases (NIAID), NIH
Improving the percentage of candidate biologic agents that make it to the market as vaccines or therapeutic products remains a significant challenge to the Biopharmaceutical Industry. One strategy that has been employed by the larger Manufacturers is to limit their risk exposure by leaving the early developmental work to small businesses and private investigators who must compete for ever shrinking private and public resources to get their candidate products into the clinic for human trials. The chances of success are particularly limited for biologic products because they must be developed in a more complex regulatory environment and at great cost. This presentation discusses issues that need to be considered in establishing a product development strategy that will promote a favorable outcome. The regulations that directly impact biologics approval will also be discussed, and Operational components of the Food and Drug Administration (FDA) that are directly responsible for the review and approval of biologic products as well as the relationship between them will be explored. |
8:35 Enhanced Efficiency of a Commercial Viral Vaccine Production Platform by Process Intensification
Ciska Dalm, Ph.D., Scientist, Upstream Processing, Crucell Holland BV
The presentation will describe the development status of an efficient market-scale manufacturing process for a recombinant adenovirus (rAd) -based tuberculosis vaccine produced on PER.C6® cells, currently in Phase I clinical trials. At least 15 batches at 10,000L scale will be required to meet the global tuberculosis vaccine market demands of 100-200 million doses after licensure. To decrease Cost of Goods and avoid early investments in a large-scale GMP facility, the focus is on a 5-10 fold intensification of the bioreactor process to be realized through increases in both unit and volumetric productivities. This work will likely provide additional insights into the propagation of eukaryotic viruses in PER.C6® cells and reveal attributes in addition to growth to high cell density under serum free conditions that position PER.C6® as an attractive cell substrate for 2nd generations of vaccines that are currently propagated with serum-containing media on cell substrate-dependent cell lines.
9:05 Antigen-Antibody Complexes as Preventive and Therapeutic Vaccines
Yu-mei Wen, Ph.D., Professor & Director, Institute of Medical Microbiology, Fudan University, Shanghai, China and Chair of the Scientific Board of Key Laboratory of Medical Molecular Virology, Ministry of Education/Ministry of Health
Our group has developed a therapeutic vaccine by complexing the current HB vaccine with a high-titer of human anti-HBs immunoglobulin. We thereby induce a higher titer of anti-HBs immune responses in adults, compared to that of using the current HB vaccine alone. This approach has been shown to induce a normal antibody response in low responder mice. In addition, HBsAg-HBIG has been used to treat chronic hepatitis B patients and has shown its effectiveness by converting serum HBeAg positive patients to anti-HBe positive and decrease viral load. We propose the use of a microbial neutralizing antigen or antigenic epitope(s) complexed to its antibodies that can be developed into vaccines with high potency for non-responders, immune incompetent individuals, and the elderly. This vaccine can also be used for treating microbial persistently infected patients or even cancer patients. We have already completed phase II HBsAg-HBIG therapeutic vaccine in a double -blind-placebo controlled clinical study in 242 patients, and Phase III clinical trial is underway.
9:35 FEATURED PRESENTATION
Novel Incentives and Partnership Models for the Development of Vaccines for Developing Countries
Douglas Holtzman, Ph.D., Senior Program Officer, Infectious Diseases Global Health Program, Bill & Melinda Gates Foundation
10:05 Coffee Break
DELIVERY
10:45 An Investigation into Colonic Vaccination
Sudaxshina Murdan, Ph.D., Senior Lecturer, Pharmaceutics, and Fellow, Higher Education Academy, The School of Pharmacy, University of London
In our laboratories, we are investigating vaccination targeted to the colon. βTCR+, in contrast to CD8+ and γδ TCR+ in the small intestine.α We postulate that colonic vaccination may turn out to have different applications to the more commonly studied oral vaccination due to the significantly different immune environments in the small and large intestines. For example, colonic intraepithelial lymphocytes are predominantly CD4+ and A preponderance of IgA2 cells over IgA1 cells is
seen in the colon (as in the rectum and in the vagina), in contrast to a predominance of IgA1 cells in the small intestine. In addition, the induction of immune responses to bacterial antigens is thought to preferentially occur in the colon. Thus, the colon might prove to be a more appropriate site of vaccination against enteric bacteria, sexually- and vertically- transmitted diseases and colorectal tumours, where antibody responses in the colon and/or rectum and genital tracts are desired. We therefore investigated the antibody levels (serum IgG and mucosal IgA) generated in response to antigen administered colonically or orally, in the mouse model. Colonic antigen administration (via the rectum) generated significantly higher levels of antigen-specific serum IgG and IgA levels in faecal and colonic extracts and in the vaginal wash compared to oral antigen administration (by gavage).Smaller differences were seen in the small intestinal IgA levels. This reflects the compartmentalisation within the common mucosal immune system and suggests that the colon may be an appropriate vaccination target for diseases of the colon, and for sexually- and vertically- transmitted diseases.
11:15 Nasal Powder: A New Approach to Vaccine Delivery
Yawei Ni, Ph.D., Chief Scientific Officer, DelSite Biotechnologies Inc.
Most infectious agents enter the body through mucosal surfaces. Nasal mucosa is easily accessible for vaccine administration and offers several advantages. Nasal immunization not only provides systemic IgG response, but also IgA response on mucosal surfaces (such as respiratory and vaginal), thus also providing the protection at the site of entry. The presentation will cover development of a nasal powder delivery platform (GelVacTM) for vaccines. This platform does not use any immunostimulatory adjuvant, but uses a novel in-situ gelling polysaccharide (GelSite® polymer) as a key functional excipient. This polymer allows the powder particles change into gel particles, providing the sustained antigen release and prolonged nasal residence time and thereby enhancing the immune response. The immunogenicity of influenza and HPV-VLP vaccines (human papillomavirus virus virus-like particle) based on this platform has been demonstrated in animals. An influenza vaccine with GelVac powder has shown room-temperature stability for 36 months (ongoing). The GelVac nasal powder is designed to provide distinct potential advantages, including room temperature stability, prolonged shelf life, and no need for cold storage and distribution, preservatives, and needles. Thus, nasal powder vaccines based on this platform will not only be effective, but also provide important logistic advantages that are critically needed for long-term storage, distribution, and administration in both developed and underdeveloped areas.
11:45 Nanoencapsulation of Vaccine Antigens for Improved Delivery
Trevor Castor, Ph.D., CEO, Aphios Corporation
Biodegradable polymer nanospheres can also be utilized for the controlled release of potent vaccine antigens. The use of SuperFluids reduces exposure of vaccine antigens to potentially denaturing organic solvents such as methylene chloride and ethyl acetate, and improves the stability of vaccine antigens in the body at ambient temperature for long periods, thereby enhancing the capability of nanoencapsulated vaccine antigens to induce the production of protective and neutralizing antibodies. Other benefits include adjuvant stimulation of the immune system by the nanospheres, and improved shelf stability of the vaccine preparation. This controlled release vaccine delivery technology has the capability to deliver different types and combinations of HIV or Influenza vaccine candidates including whole inactivated virus particles, DNA plasmids and/or subunit protein antigens.
12:15pm Lunch on Your Own (Lunch Workshop Sponsorship Available)
1:45 Chairperson's Remarks
Tarek Fahmy, Ph.D., Assistant Professor, Biomedical Engineering, Yale University
1:50 Application of New Insights in Immunology to Vaccine Development
Alan Shaw, Ph.D., President & CEO, VaxInnate, Inc.
Information generated over the past 7 years has altered the way we think about vaccine antigen delivery and processing. Knowledge about Toll-Like Receptors and Nucleotide Oligomerization Domain-like Receptors provides hints about how to increase vaccine potency while at the same time, maintaining safety. Several clinical trials of vaccines based on these principles are underway, and I will present the resultant data from these trials.
2:20 Novel Vaccines by Gene Transfer
Frank Tung, Ph.D., President & CEO, GeneCure Biotechnologies
Lentiviral vector is effective in delivering genes encoding antigens to immune system and elicits both strong antibody and cell-mediated immune responses. Most importantly, lentiviral vector-based vaccines can be repeatedly used as therapeutic vaccines to treat chronic infectious diseases and cancers.
2:50 Refreshment Break
3:30 PLENARY SESSION – INTERACTIVE PANEL DISCUSSION
- The Critical Business Challenges Associated With Vaccine Trials
- Reducing costs without compromising safety
- Conducting trials in developing countries
- Novel manufacturing platforms for vaccines & cell cultures
- Applying adaptive trial design to vaccine trials
Moderator:
Frank Malinoski, M.D., Ph.D., Senior Vice President, Medical and Scientific Affairs, MedImmune, Inc.
Panelists:
- Karen A. Near, M.D., M.S., Medical Director, Clinical Development & Immunologic Products, Baxter Vaccines
- Danilo R. Casimiro, Ph.D., Director, Vaccine & Immunologic Products, Merck Research Laboratories
5:00 End of “Novel Vaccines” Conference
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