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
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.
Knowable unknowns along the path to effective vaccines for HIV, malaria and other global health challenges
Dr Chris Wilson, Bill & Melinda Gates Foundation, USA
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.
Getting new vaccines to people who need them
Dr Rino Rappuoli, Novartis Vaccines, Italy
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.