Differential ability of specific regions of Plasmodium falciparum sexual-stage antigen, Pfs230, to induce malaria transmission-blocking immunity

Antibodies raised against an Escherichia coli-produced recombinant protein encoding a 76-kDa section (region C) of malaria transmission-blocking vacci ne candidate, Pfs230, have previously been shown to significantly reduce th e ability of Plasmodium falciparum parasites to infect mosquitoes (71.2-89. 8%). To further define the region of the Pfs230 required for transmission-b locking activity, four recombinant proteins each encoding a section of regi on C (Pfs230 amino acids 443-1132) were produced using the same E. coli exp ression system and tested for immogenicity in mice: (i) r230/MBP.C5' encode s the first half of region C (amino acids 443-791, six cysteines); (ii) r23 0/MBP.CM1 encodes only cysteine motif (CM) 1 (amino acids 583-913, eight cy steines); (iii) r230/MBP.C1.6 (amino acids 453-913, eight cysteines) also i ncludes all of CM1; and (iv) r230/MBP.C2 encodes only CM2 (amino acids 914- 1268, 11 cysteines). All the recombinant proteins induced antibodies that r ecognized parasite-produced Pfs230, but the titre of the Pfs230 specific-an tibodies generated varied, C = C1.6 = C5' > CM1 > CM2. Two recombinants, r2 30/MBP.C5' and r230/MBP.C1.6, induced antibody titres that were equivalent to or greater than the titre generated by r230/MBP.C. However, in contrast to r230/MBP.C, none of the recombinants induced antibodies that effectively blocked parasite infectivity to mosquitoes. This suggests that the inclusi on of amino acids 914-1132 is important for the production of the transmiss ion-blocking epitope present in region C.