title: Immunogenicity of the C-terminal 19-kDa fragment of the Plasmodium falciparum merozoite surface protein 1 (MSP1), YMSP1(19) expressed in S. cerevisiae.
abstract: The immunogenicity of the C-terminal 19-kDa fragment of Plasmodium falciparum MSP1 expressed in yeast as a nonfusion product, YMSP1(19), was studied. Immunization with YMSP1(19) in rabbits induced high titers 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 MSP1(19) in a genetically diverse population. Although YMSP1(19) 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 MSP1(42) (BVp42), which contains the entire MSP1(19) coding sequence. Further analyses showed that YMSP1(19) was the target of the inhibitory, anti-BVp42 Abs because YMSP1(19) could completely block binding of anti-BVp42 Abs to parasite MSP1 or BVp42. Moreover, depletion of YMSP1(19)-specific Abs completely abolished the parasite inhibitory activities of anti-BVp42 sera. Anti-YMSP1(19) sera did not block the inhibitory activities of anti-BVp42 sera, suggesting that inhibitory epitopes were not in close structural proximity with noninhibitory epitopes. The finding that YMSP1(19) possessed inhibitory epitopes but induced anti-MSP1 Abs that were not inhibitory suggests that although the T-epitope(s) produced by immunization with YMSP1(19) could provide help for Ab production, it did not induce an effective inhibitory Ab response. We hypothesize that the nature/specificity of T helper epitopes on MSP1 may be crucial in efficient induction of biologically relevant and/or protective Abs.
authors.affiliation: Department of Tropical Medicine, University of Hawaii, Honolulu 96816.
authors.forename: G S
authors.initials: GS
authors.lastname: Hui
authors.forename: W L
authors.initials: WL
authors.lastname: Gosnell
authors.forename: S E
authors.initials: SE
authors.lastname: Case
authors.forename: C
authors.initials: C
authors.lastname: Hashiro
authors.forename: C
authors.initials: C
authors.lastname: Nikaido
authors.forename: A
authors.initials: A
authors.lastname: Hashimoto
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D020066:Merozoite Surface Protein 1; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011498:Protein Precursors / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D013045:Species Specificity
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins