Four potential target antigens (Pfs25/Pgs25, Pfs40, Pfs230, and Pgs28) of transmission-blocking antibodies have now been cloned in our laboratory, and a fifth (chitinase) has been identified. Of the four target antigens that have been cloned, all have been expressed in one or more recombinant expression systems, but only recombinant Pfs25 has induced transmission- blocking antibodies in laboratory animals. Our immediate goals are to 1) test in humans the safety, immunogenicity, and efficacy of a Pfs25 subunit vaccine and design a means of testing the efficacy of such a transmission- blocking vaccine in the field; 2) determine the role, if any, that the calcium-binding Pfs40 plays in sexual development and ascertain if Pfs40 is a target of transmission-blocking antibodies; 3) identify and express as recombinant protein the B-cell epitopes in Pfs230 responsible for the transmission-blocking activity of our monoclonal antibodies to Pfs230; 4) isolate the gene from P. falciparum encoding the protein analogous to the P. gallinaceum Pgs28; 5) determine if antibodies to chitinase completely block transmission, and if so, isolate and express the gene encoding this ookinete enzyme; and 6) isolate analogous genes (if they exist) to these five proteins from the other human malaria parasites. Our more long term goals include identifying new target antigens on sexual stage parasites, and defining the molecular mechanisms involved in fertilization of malarial parasites.
