Development of malaria vaccines: memorandum from a USAID/WHO meeting.

The fifth meeting of the Scientific Working Group on the Immunology of Malaria evaluated studies of the production and analysis of defined malarial antigens. Rapid progress has been made in the study of protective antigens on the surface of sporozoites and it is likely that a family of analogous polypeptides occurs in several species of Plasmodium. New assays have been developed for the detection of these antigens and for the detection of infected mosquitos. Exoerythrocytic stages of several parasite species can be cultivated in vitro, providing an assay system for antibody and allowing the characterization of exoerythrocytic stage antigens. Progress has also been made in the identification of species- and stage-specific antigens of the asexual blood stages of rodent, simian, and human malaria parasites. In some instances, protective immunity has been shown to be directed against polypeptides (with a high relative molecular mass) synthesized at a late stage of schizont development. Messenger RNA (mRNA) species from P. knowlesi and P. yoelii have been successfully translated in vitro to give polypeptides with a high relative molecular mass (M(r)). Monoclonal antibodies have been used to identify and to purify important parasite antigens and purified P. yoelii antigens induced protective immunity. Monoclonal antibodies reactive with merozoite surface antigens have been used, as well as S-antigens, to distinguish between different isolates of P. falciparum. Recombinant DNA technology is being applied to Plasmodium: differences were found between repetitive DNA sequences from the genome of two isolates of P. falciparum; the genes for ribosomal RNA of P. falciparum and P. yoelii, and sequences homologous to the actin gene were identified in fragments of Plasmodium DNA cloned in prokaryotic vectors; by means of hybrid selection, complementary DNA (cDNA) probes were used to purify mRNAs encoding proteins of P. knowlesi of up to 100 000 M(r).