Identifying the knowledge gap in vaccine development against blood stage Plasmodium falciparum malaria

Plasmodium falciparum causes the most severe form of malaria in humans which annually kills in excess of a million people and results in significant morbidity in countless others. A scourge of mankind since prehistory, this protozoan parasitic disease thus continues to present a leading global public health challenge across tropical regions in which it is endemic. Manufacture of an effective vaccine against the pathogenic asexual blood stages of P. falciparum would have a profound impact in preventing malaria-associated deaths in developing countries worldwide, especially of children younger than 5 years of age and pregnant women. In adults living under conditions of endemicity who are exposed repeatedly to P. falciparum immunity is acquired gradually over several years. This may not achieve sterile immunity, eliminating parasites from the body, but at the very least reduces parasitemia to below a clinical threshold. Given this natural precedent, one aspect of antimalarial vaccine strategy is predicated on how artificial immunization can be induced rapidly to simulate, and indeed boost, such protection. Among the obstacles hampering successful vaccine design is an insufficient understanding of the precise types of immune response for which to aim and what antigens elicit protective immunity. This article discusses the knowledge gap that exists in approaches to develop an asexual blood stage vaccine, identifying some of the key questions to which answers are sought.