Differential evidence of natural selection on two leading sporozoite stage malaria vaccine candidate antigens.


Weedall, GD; Preston, BM; Thomas, AW; Sutherland, CJ; Conway, DJ; (2007) Differential evidence of natural selection on two leading sporozoite stage malaria vaccine candidate antigens. International journal for parasitology, 37 (1). pp. 77-85. ISSN 0020-7519 DOI: https://doi.org/10.1016/j.ijpara.2006.09.001

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Abstract

Experimental malaria vaccines based on two sporozoite stage candidate antigens of Plasmodium falciparum, the circumsporozoite protein (CSP) and thrombospondin-related adhesive protein (TRAP), have undergone clinical trials of efficacy. The relevance of naturally existing polymorphism in these molecules remains unknown. Sequence polymorphism in the genes encoding these antigens was studied in a Gambian population (sample of 48 trap and 44 csp gene sequences) to test for signatures of selection that would result from naturally acquired immunity. Allele frequency distributions were analyzed and compared with data from another population (in Thailand). Patterns of non-synonymous and synonymous polymorphism in P. falciparum and in Plasmodium vivax were compared with divergence from related species. Results indicate that polymorphism in TRAP is under strong selection for amino acid sequence diversity and that allele frequencies are under balancing selection within the Gambian P. falciparum population. There was no such evidence for CSP, calling into question the idea that most polymorphisms in this gene are under immune selection. There was a weak trend for regions known to encode T cell epitopes to have slightly higher indices suggesting balancing selection. Overall, the results predict more allele-specific immunity to TRAP than to CSP and should be considered in design and efficacy testing of vaccine candidates based on these antigens.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 17046771
Web of Science ID: 243663500008
URI: http://researchonline.lshtm.ac.uk/id/eprint/10820

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