Four potential target antigens (Pfs25/Pgs25, Pfs28, Pfs40, and Pfs230) of transmission-blocking antibodies have now been cloned in our laboratory, and a fifth ( parasite-produced chitinase) and a sixth (a mosquito-produced protease) have 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 (rPfs25) 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) express Pfs28 as a recombinant protein in a form that elicits transmission- blocking antibodies and test various combinations of rPfs25 and rPfs28 in a cocktail vaccine to determine if the combination elicits longer lasting or higher titer transmission-blocking antibodies, 3) 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, 4) identify and express as recombinant protein the B-cell epitopes in Pfs230 responsible for the transmission-blocking activity of our monoclonal antibodies to Pfs230, 5) determine if antibodies to parasite-produced chitinease or mosquito-produced protease completely block transmission, and if so, isolate and express the genes encoding these enzyme, and 6) isolate analogous genes to these five parasite proteins, if they exist, from P. vivax. 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.
