The development of malaria vaccines: SPf66--what next?

Malaria, especially that caused by Plasmodium falciparum, is the most important parasitic disease of man. The complexity of the life cycle, the transmission dynamics in different endemic settings, and the spread of resistance to various drugs by the parasite and to insecticides by the vector render control strategies very difficult. An effective vaccine against malaria would represent a major strengthening of control. Research efforts to identify and select antigens for vaccine development have been substantial, particularly in the past 20 years. Various molecules from the pre-erythrocytic, asexual blood and sexual stages have been described and tested in experimental systems, and some may become interesting vaccine candidates. A crucial step was taken with the development of SPf66, a synthetic polypeptide based on pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. The concept of the SPf66 vaccine is not the prevention of clinical malaria but reduction of morbidity, and it is thus suitable for endemic areas, particularly Africa. The clinical phase III trials so far undertaken in Latin America and in Africa have clearly documented the safety, immunogenicity and partial efficacy of SPf66 against clinical malaria. The efficacy estimates of all trials are below those we generally demand from vaccines and when we aim to induce sterile immunity. Therefore, a large number of issues at the field and laboratory levels, such as ways of optimizing efficacy (doses, timing, age of vaccination), and understanding the mechanisms of action and effectiveness, need to be investigated before one can consider the public health use of SPf66 as a component of an integrated malaria control programme. The substantial tasks ahead involve (1) improving the vaccine which we have and (2) devising and testing new vaccines which may prove more efficacious. Malaria vaccines are now a reality, and the achievements of SPf66 to date, the ongoing research efforts with other vaccine candidates, and the potential of DNA vaccines make it possible to predict that widespread use of an efficacious vaccine no longer represents an unrealistic target.