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J Infect Dis. 2007 Jan 15;195(2):279-87. Epub 2006 Dec 13.

Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection.

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  • 1Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Abstract

BACKGROUND:

Plasmodium falciparum merozoite surface protein (MSP) 3 is an asexual blood-stage malaria vaccine candidate antigen. Sequence polymorphisms divide alleles into 2 major types, but the adaptive and immunological significance of the types has not been defined.

METHODS:

One hundred one msp3 allele sequences were sampled from 2 populations living in areas where malaria is endemic and were analyzed for evidence of natural selection. Recombinant antigens representing full-length sequences of different allelic types and a relatively conserved C-terminal region were produced, to evaluate immunization-induced antibody responses in mice and protective associations for naturally acquired antibodies in a cohort of 319 Gambian children under surveillance for malaria.

RESULTS:

Frequency-based statistical analyses indicated that polymorphisms are maintained by balancing selection in each of the 2 populations studied. Immunization of mice with full-length MSP3 antigens induced predominantly type-specific antibodies, and a large proportion of naturally acquired antibodies to MSP3 in humans also discriminated between the alleles. Among Gambian children, antibodies to allele-specific and conserved epitopes in MSP3 were associated prospectively with protection from clinical malaria, even after adjustment for age and for the presence of antibodies to other merozoite antigens.

CONCLUSIONS:

A vaccine incorporating both major allelic types of this promising candidate antigen could be particularly useful for induction of protective immunity in infants and young children.

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PMID:
17191173
[PubMed - indexed for MEDLINE]
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