Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection.
| Autor: | Polley SD; Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom., Tetteh KK, Lloyd JM, Akpogheneta OJ, Greenwood BM, Bojang KA, Conway DJ |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of infectious diseases [J Infect Dis] 2007 Jan 15; Vol. 195 (2), pp. 279-87. Date of Electronic Publication: 2006 Dec 13. |
| DOI: | 10.1086/509806 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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