Session 4: Prospects for better vaccines and vaccination strategies in low-income countries
Developing vaccines against enteric infections in developing countries
Professor Cecil Czerkinsky, Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Sophia-Antipolis, France
Abstract
As of today, all vaccines but one (oral polio vaccine) recommended by the Expanded Program on Immunization are administered by way of injections. As such, these vaccines induce immunity in blood and in peripheral tissues but are relatively inefficient for eliciting immune responses in mucosal tissues such as the gastrointestinal tract, the target of enteric infections. On the other hand, mucosal (oral, sublingual, nasal, rectal) administration of a number of experimental as well as few licensed enteric vaccines have been shown to be more efficient for inducing mucosal intestinal immune responses in animals and in humans. Modern biotechnology has yielded an abundance of mucosal vaccine candidates against enteric infections but only few vaccines have been registered for human use, albeit in certain age groups. Extensive efforts are being deployed to design new and safe adjuvants for mucosal immunisation, to identify alternative delivery routes, and to develop new vectors and carrier/delivery systems for tissue- and cell-specific targeting of vaccines. If these candidates are to ultimately reach those in need in developing countries, several lessons from clinical and field research done in these settings must be considered. These lessons include the need to develop vaccines that avoid the need for storage in a cold chain and that can be administered without needles or expensive delivery devices. These vaccines must be safe and work in the world’s poorest, including undernourished children, and must be able to contain epidemics following complex emergencies. Finally, an ideal mucosal vaccine should confer long-term protection and especially herd immunity.
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Professor Cecil Czerkinsky, Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Sophia-Antipolis, France
Professor Cecil Czerkinsky, Institut de Pharmacologie Moleculaire et Cellulaire, CNRS-INSERM-University of Sophia-Antipolis, France
Cecil Czerkinsky, DMD, PhD, Dr Med Sci, graduated from Nice and Lyon Medical and Dental Schools (France) and from Göteborg Medical Faculty (Dr Med Sci).
After postdoctoral stays in the UK and US, Czerkinsky established a laboratory of Mucosal Immunology at Göteborg University, which he led from 1989 to 1998. In 1998, Dr Czerkinsky was appointed Research Director at INSERM (French National Institute of Health) in Nice, France and spearheaded a research program dedicated to Vaccination and Mucosal Immunity. From 2005 to 2012, he was Deputy Director General of the International Vaccine Institute in Seoul, South Korea, where he served as head of the R&D program. Professor Czerkinsky has been adviser for several supranational and national health or biomedical research agencies as well as foundations and pharmaceutical corporations. He has published over 180 articles in the areas of experimental and clinical immunology with a focus on mucosal vaccines. Cecil Czerkinsky currently serves as Research Director at the Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), a joint CNRS-INSERM-University research center located in Sophia-Antipolis on the French Riviera.
Knowable unknowns along the path to effective vaccines for HIV, malaria and other global health challenges
Dr Chris Wilson, Bill & Melinda Gates Foundation, USA
Abstract
Animal models can help to elucidate the principles of host pathogen interactions and to gain initial insights regarding the immunogenicity, safety and possible protective efficacy of vaccines. However, their predictive power is limited and few are truly fit for purpose. Hence, there is no substitute for human trials for testing new vaccine concepts and making decisions about whether vaccine concepts and candidates should advance. Historically, human testing of new vaccine concepts has been largely limited to just those decisions, with little attention to understanding the causal mechanisms for failure or partial but insufficient efficacy. Done in the name of reducing costs, such approaches lead to excessive costs and delays when addressing the most intractable of diseases, such as HIV, TB and malaria for which vaccines have to be more effective than naturally acquired immunity and the probability of success for candidates is low. New systems approaches and more nimble human exploratory test of concept trials provide the opportunity to better illuminate these causal mechanisms at an early stage and to thereby foster a more rapid, iterative cycle of vaccine improvement before embarking upon large, late stage clinical trials with suboptimal candidates.
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Dr Chris Wilson, Bill & Melinda Gates Foundation, USA
Dr Chris Wilson, Bill & Melinda Gates Foundation, USA
Chris Wilson, Director of the Global Health Discovery & Translational Sciences program, leads a team that targets fundamental scientific and technological advances in global health that could lead to new ways to prevent, treat, and diagnose disease. Prior to joining the Gates Foundation in 2009, he was a member of the faculty at the University of Washington from 1979-2009, where he served as head of the Division of Infectious Diseases, Immunology and Rheumatology, Department of Pediatrics from 1989-1999, then as Chairman of the Department of Immunology and head of the graduate program in immunology from 1999-2009. He has served on a number of national advisory panels, including the Institute of Medicine Vaccine Safety Review Committee (2001-2004) and the Advisory Council, National Institute of Child Health and Human Development, National Institutes of Health (NIH). He is a member of the Advisory Committee to the Director, NIH and the Advisory Council of the National Institute of Allergy & Infections Diseases (as of November 2013). He is an elected fellow of the American Association for the Advancement of Science. Wilson received a bachelor’s degree from the University of California, Irvine and a medical degree from UCLA. He trained in pediatrics at Boston Children’s Hospital /Harvard Medical School, served in the US Public Health Service, and then was a post-doctoral fellow in infectious diseases while performing immunology research at Stanford University.
Getting new vaccines to people who need them
Dr Rino Rappuoli, Novartis Vaccines, Italy
Abstract
Thanks to the Global Alliance for Vaccines and Immunisation (GAVI), the Vaccine Fund, and the Bill and Melinda Gates Foundation, we have made enormous progress in providing already existing vaccines to developing countries. However, we are still struggling to develop those vaccines for which there is no market in the western world, because there is no incentive for the private sector to justify the investments necessary for vaccine development. In many cases we have the technologies, but not the resources to develop these vaccines. The present emergency with the Ebola vaccine provides an excellent example where a vaccine was feasible several years ago, but we waited for a humanitarian disaster to rush a vaccine into development.
Several institutions dedicated to the development of vaccines against diseases present only in low-income countries emerged during the last few years. These include the International Vaccine Institute, Korea, the Novartis Vaccines Institute for Global Health, Italy, the Hillemann Institute, India, the Sabin Vaccine Institute, and the Infectious Disease Research Institute, USA. Nevertheless, solving this problem requires a much more significant global effort than what we have now, including a clear policy, global coordination of funds dedicated to development of orphan vaccines, agreement on regulatory strategies and incentives for the private sector.
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Dr Rino Rappuoli, Novartis Vaccines, Italy
Dr Rino Rappuoli, Novartis Vaccines, Italy
Rino Rappuoli is Global Head Research and Development at Novartis Vaccines and is based in Siena, Italy. He earned his PhD in Biological Sciences at the University of Siena and has served as visiting scientist at Rockefeller University in New York and Harvard Medical School in Boston. Prior to the present position he was head R&D of Sclavo and then head of vaccine research and Chief Scientific Officer of Chiron Corporation.
Several molecules he worked with became part of licensed vaccines. These include: CRM197 used in H.influenzae, N.meningitidis, and pneumococcus vaccines; PT9K/129G, a genetically detoxified pertussis toxin used for an acellular vaccine against pertussis; the first conjugate vaccine against meningococcus C and later against meningococcus ACYW; the MF59 adjuvant used in seasonal and pandemic influenza vaccines and the FHBP, NadA and NHBA antigens derived from the genome of meningococcus B that made possible the development of Bexsero.
He was elected member of the US National Academy of Sciences (NAS) and the European Molecular Biology Organization (EMBO). Awards conferred include: Paul Ehrlich and Ludwig Darmstaedter Prize (1991), the Gold Medal by the Italian President (2005), the Albert B. Sabin Gold Medal (2009), the Lifetime Achievement Award from the Institute of Human Virology in Maryland (2010), and the Excellence Award from the European Society of Clinical Microbiology and Infectious Diseases (2011). In 2013 he was nominated third most influential person worldwide in the field of vaccines (Terrapin). He has introduced several novel scientific concepts (genetic detoxification, 1987, cellular microbiology, 1996; reverse vaccinology, 2000; pangenome, 2005, structural vaccinology, 2008).