Immunological cross-reactivity of the C-terminal 42-kilodalton fragment of Plasmodium falciparum merozoite surface protein 1 expressed in baculovirus.
The roles of allelic and conserved epitopes in vaccine-induced immunity to the C-terminal 42-kDa fragment of the Plasmodium falciparum merozoite surface protein 1 (MSP1) were investigated. The C-terminal fragment of MSP1 was expressed as a baculovirus recombinant protein, BVp42. Rabbits were immunized with BVp42, and antibodies were tested for reactivity to MSP1s of the homologous and heterologous allelic forms, represented by the FUP, FVO, FC27, and Honduras parasite isolates, by enzyme-linked immunosorbent assay and indirect immunofluorescence antibody assay. Despite the fact that allelic sequences accounted for approximately 50% of the BVp42 molecule, anti-BVp42 antibodies cross-reacted extensively with parasites carrying heterologous MSP1 alleles. Enzyme-linked immunosorbent inhibition assays confirmed that an overwhelming majority of the anti-BVp42 antibodies were cross-reactive, suggesting that determinants within conserved block 17 are dominant B-cell epitopes in the anti-BVp42 response. Moreover, the BVp42 polypeptide could inhibit (> 90%) the cross-reactivity of anti-MSP1 antibodies in animals immunized with the complete native MSP1 protein. Anti-BVp42 antibodies were equally effective in inhibiting the in vitro growth of parasites carrying homologous or heterologous MSP1 alleles. Serotyping by monoclonal antibodies indicated that the immunological and biological cross-reactivities were not caused by identical variant-specific amino acid substitutions within conserved block 17. These results should provide the impetus to develop a vaccine based on the C-terminal conserved region(s) of MSP1 against parasites of diverse genetic makeup.
Hui
G S
GS
Department of Tropical Medicine, University of Hawaii, Honolulu 96816.
Hashiro
C
C
Nikaido
C
C
Case
S E
SE
Hashimoto
A
A
Gibson
H
H
Barr
P J
PJ
Chang
S P
SP
D000483:Alleles; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments / Q000096:biosynthesis / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins; D011994:Recombinant Proteins