The contribution of molecular biology to our understanding of malaria

The search for a vaccine against malaria has led to a concerted effort to understand the structure and function of many malaria proteins, as well as their capacity to induce host protective responses. The numerous constraints of working with the various malarial species has spurred the early and widespread adoption of the techniques of recombinant DNA technology. Consequently, we know a great deal about the primary structure of many malarial proteins, particularly those of P. falciparum. In particular, we know a great deal about the variant forms of several important vaccine candidates such as the merozoite proteins MSP-1, MSP-2 and AMA-1, information that will be useful for the formulation of vaccines that can be used worldwide. Less is known about the function of these proteins, and this remains an urgent need if new therapies aimed at interfering with key parasitic processes such as invasion of red cells and cytoadherence are to be developed. A great deal of effort has been expended in developing expression and delivery systems that can produce malarial proteins in abundant amounts and in the correct conformation, in order to induce effective, high titre immune responses reliably in people with diverse histocompatability status. The recent development of DNA-based vaccines appears particularly promising. Significant advances have been made in our understanding of the mechanisms of parasite resistance to drugs, although development of new drug targets has been less successful. A recently inaugurated malaria genome project is taking the first steps towards providing a complete physical map of the malaria genome and ultimately the complete genomic sequence. Notwithstanding the many insights provided by molecular biological studies of parasites, the conventional armoury of drugs and control programmes of various sorts appears likely to remain our major defence against malaria for some time to come.