Allelic diversity and antibody recognition of Plasmodium falciparum merozoite surface protein 1 during hypoendemic malaria transmission in the Brazilian Amazon region

The polymorphic merozoite surface protein (MSP-1) of Plasmodium falciparum is a major asexual blood-stage malaria vaccine candidate. The impact of all elic diversity on recognition of MSP-1 during the immune response remains t o be investigated in areas of hypoendemicity such as the Brazilian Amazon r egion. In this study, PCR was used to type variable regions, blocks 2, 4, a nd 10, of the msp-1 gene and to characterize major gene types (unique combi nations of allelic types in variable blocks) in P. falciparum isolates coll ected across the Amazon basin over a period of 12 years. Twelve of the 24 p ossible gene types were found among 181 isolates, and 68 (38%) of them had more than one gene type. Temporal, but not spatial, variation was found in the distribution of MSP-1 gene types in the Amazon. Interestingly, some gen e types occurred more frequently than expected From random assortment of al lelic types in different blocks, as previously found in other areas of ende micity. We also compared the antibody recognition of polymorphic (block 2), dimorphic (block 6), and conserved (block 3) regions of MSP-1 in Amazonian malaria patients and clinically immune Africans, using a panel of recombin ant peptides. Results were summarized as follows, (i) All blocks were targe ted hy naturally acquired cytophilic antibodies of the subclasses IgG1 and IgG3, but the balance between IgG1 and IgG3 depended an the subjects' cumul ative exposure to malaria. (ii) The balance between IgG1 and IgG3 subclasse s and the duration of antibody responses differed in relation to distinct M SP-1 peptides. (iii) Antibody responses to variable blocks 2 and 6 mere pre dominantly type specific, but variant-specific antibodies that target isola te-specific repetitive motifs within block 2 were more frequent in Amazonia n patients than in previously studied African populations.