INDUCTION OF ANTIBODIES TO THE PLASMODIUM-FALCIPARUM MEROZOITE SURFACE PROTEIN-1 (MSP1) BY CROSS-PRIMING WITH HETEROLOGOUS MSP1S

The merozoite surface protein-1 (MSP1) of Plasmodium falciparum posses ses intervening conserved and nonconserved sequences. The relative imp ortance of these sequences in providing T cell help for Ab production was investigated in a series of cross-priming studies using homologous and heterologous parasite MSP1 proteins. Cross-priming with heterolog ous MSP1s was as efficient as homologous immunizations in inducing ant i-MSP1 Abs. Similar to homologous immunization, cross-priming with het erologous MSP1s induced primarily Abs to conserved epitopes. The speci ficities of the Abs were also similar for the two immunization regimen s. Studies were also performed with use of the C-terminal p42 fragment of MSP1 expressed in baculovirus (BVp42). When BVp42 was used either as the priming Ag followed by boosting with homologous (or heterologou s) MSP1 or as the booster Ag after priming with homologous (or heterol ogous) MSP1, much lower anti-BVp42 Ab titers were produced compared wi th priming/boosting with homologous or heterologous MSP1s or BVp42 alo ne. Thus, immunization with the complete parasite MSP1 induced a domin ant, conserved Th epitope(s) specific for anti-p42 Ab production, and such determinant(s) was either located outside the p42 region or was n ot provided by the BVp42 because of possible differences in the proces sing of parasite MSP1 vs BVp42. Our data provided a strong rationale t o identify and include conserved Th epitope(s) in MSP1 vaccines. Furth ermore, a MSP1 vaccine on the basis of the C-terminal p42 fragment may benefit by the inclusion of additional Th epitopes to achieve effecti ve boosting in the field.