Identification of a Conserved Region of Plasmodium falciparum MSP3 Targeted by Biologically Active Antibodies to Improve Vaccine Design
Singh, Subhash ; Soe, Soe ; Mejia, Juan-Pedro ; Roussilhon, Christian ; Theisen, Michael ; Corradin, Giampietro ; Druilhe, Pierre
In: Journal of Infectious Diseases, 2004, vol. 190, no. 5, p. 1010-1018
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- 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-crossreactive 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