Immunogenicity of the C-terminal 19-kDa fragment of the Plasmodium falciparum merozoite surface protein 1 (MSP1) , YMSP1 (19) expressed in S. cerevisiae
Hui, G.S.; Gosnell, W.L.; Case, S.E.; Hashiro, C.; Nikaido, C.; Hashimoto, A.; Kaslow, D.C.
Journal of Immunology 153(6): 2544-2553
1994
ISSN/ISBN: 0022-1767 PMID: 8077664 Document Number: 432525
The immunogenicity of the C-terminal 19-kDa fragment of Plasmodium falciparum MSP1 expressed in yeast as a non-fusion product, YMSP119, was studied. Immunization with YMSP119 in rabbits induced high titres of Abs specific for native conformational epitopes on parasite MSP1. In mice, immunogenicity was dependent on the mouse strain and the adjuvant formulation. This suggests that different adjuvants may alter the immunogenicity of MSP119 in a genetically diverse population. Although YMSP119 induced anti-MSP1 Abs, they did not inhibit in vitro parasite growth. This contrasts with the strong inhibitory activities of Abs produced against a recombinant MSP142 (BVp42), which contains the entire MSP119 coding sequence. Further analyses showed that YMSP119 was the target of the inhibitory, anti-BVp42 Abs because YMSP119 could completely block binding of anti-BVp42 Abs to parasite MSP1 or BVp42. Moreover, depletion of YMSP119-specific Abs completely abolished the parasite inhibitory activities of anti-BVp42 sera. Anti-YMSP119 sera did not block the inhibitory activities of anti-BVp42 sera, suggesting that inhibitory epitopes were not in close structural proximity with non-inhibitory epitopes. The finding that YMSP119 possessed inhibitory epitopes but induced anti-MSP1 Abs that were not inhibitory suggests that although the T-epitope(s) produced by immunization with YMSP119 could provide help for Ab production, it did not induce an effective inhibitory Ab response. The authors hypothesize that the nature/specificity of T helper epitopes on MSP1 may be crucial in efficient induction of biologically relevant and/or protective Abs.