Subunit blood-stage malaria vaccines

Abstract

The existence of asymptomatically parasitemic individuals in malaria-endemic areas has long been recognised to signify naturally acquired immunity to malaria disease, resulting from control of the parasite’s asexual blood-stage. This has for many years been viewed as a ‘proof-of-concept’ encouraging the development of blood-stage vaccines (BSVs). Results of clinical trials of candidate subunit BSVs have mostly, however, not lived up to early expectations and the field is currently experiencing a challenging period. This chapter examines the current state of BSV development and prospects for developments in the near future. The various immunological mechanisms by which BSVs might conceivably induce protection are examined, along with the means of assaying these effectors in vitro. Pre-clinical and clinical in vivo models are discussed, particularly highlighting the potential value of the blood-stage controlled human malaria infection (CHMI) model. A summary of the results of clinical trials over the last 25 years is provided, along with an overview of trials currently under way. Consistent with their prominence in the field’s efforts, vaccines targeting the Plasmodium falciparum merozoite are the main focus, but vaccines against Plasmodium vivax and PfEMP1 (including pregnancy-associated malaria) are also discussed. Finally, a personal view of possible areas for future development is presented.