Identification of a conserved region of Plasmodium falciparum MSP3 targeted by biologically active antibodies to improve vaccine design.
Merozoite surface protein 3 (MSP3) is a target of antibody-dependent cellular inhibition (ADCI), a protective mechanism against Plasmodium falciparum malaria. From the C-terminal half of the molecule, 6 overlapping peptides were chosen to characterize human immune responses. Each peptide defined at least 1 non-cross-reactive B cell epitope. Distinct patterns of antibody responses, by level and IgG subclass distribution, were observed in inhabitants of a malaria-endemic area. Antibodies affinity purified toward each peptide differed in their functional capacity to mediate parasite killing in ADCI assays: 3 of 6 overlapping peptides had a major inhibitory effect on parasite growth. This result was confirmed by the passive transfer of anti-MSP3 antibodies in vivo in a P. falciparum mouse model. T helper cell epitopes were identified in each peptide. Antigenicity and functional assays identified a 70-amino acid conserved domain of MSP3 as a target of biologically active antibodies to be included in future vaccine constructs based on MSP3.
Singh
Subhash
S
Bio-Medical Parasitology Unit, Pasteur Institute, Paris, France.
Soe
Soe
S
Mejia
Juan-Pedro
JP
Roussilhon
Christian
C
Theisen
Michael
M
Corradin
Giampietro
G
Druilhe
Pierre
P
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D015195:Drug Design; D018985:Epitopes, B-Lymphocyte; D006801:Humans; D016867:Immunocompromised Host; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines; D011994:Recombinant Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; C089133:merozoite surface protein 3, Plasmodium