Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities

Abstract

While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document.