Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia.


Pinder, M; Reece, WH; Plebanski, M; Akinwunmi, P; Flanagan, KL; Lee, EA; Doherty, T; Milligan, P; Jaye, A; Tornieporth, N; Ballou, R; McAdam, KP; Cohen, J; Hill, AV; (2004) Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia. Clinical and experimental immunology, 135 (2). pp. 286-93. ISSN 0009-9104 DOI: 10.1111/j.1365-2249.2004.02371.x

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Abstract

Vaccination of malaria-naive humans with recombinant RTS,S/AS02, which includes the C-terminus of the circumsporozoite protein (CS), has been shown to induce strong T cell responses to both the whole protein antigen and to peptides from CS. Here we show that strong T cell responses were also observed in a semi-immune population in The Gambia, West Africa. In a Phase I study, 20 adult male volunteers, lifelong residents in a malaria-endemic region, were given three doses of RTS,S/AS02 at 0, 1 and 6 months. Responses to RTS,S, hepatitis B surface antigen and peptides from CS were tested using lymphocyte proliferation, interferon (IFN)-gamma production in microcultures, and IFN-gamma ex vivo and cultured ELISPOT, before and after vaccination. Cytotoxic responses were tested only after vaccination and none were detected. Before vaccination, the majority of the volunteers (15/20) had detectable responses in at least one of the tests. After vaccination, responses increased in all assays except cytotoxicity. The increase was most marked for proliferation; all donors responded to RTS,S after the third dose and all except one donor responded to at least one peptide after the second or third dose. There was a lack of close association of peptide responses detected by the different assays, although in microcultures IFN-gamma responses were found only when proliferative responses were high, and responses by cultured ELISPOT and proliferation were found together more frequently after vaccination. We have therefore identified several peptide-specific T cell responses induced by RTS,S/AS02 which provides a mechanism to investigate potentially protective immune responses in the field.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Tropical Epidemiology Group
Vaccine Centre
PubMed ID: 14738458
Web of Science ID: 188353600016
URI: http://researchonline.lshtm.ac.uk/id/eprint/13490

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