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

M. Pinder, W. H H Reece, M. Plebanski, P. Akinwunmi, K. L. Flanagan, E. A M Lee, T. Doherty, P. Milligan, A. Jaye, N. Tornieporth, R. Ballou, K. P M J Mcadam, J. Cohen, A. V S Hill

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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)-γ production in microcultures, and IFN-γ 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-γ 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.

Original languageEnglish
Pages (from-to)286-293
Number of pages8
JournalClinical and Experimental Immunology
Volume135
Issue number2
DOIs
Publication statusPublished - Feb 2004
Externally publishedYes

Keywords

  • Cell-mediated
  • Circumsporozoite
  • ELISPOT
  • Immunity
  • Plasmodium falciparum vaccine

Cite this

Pinder, M., Reece, W. H. H., Plebanski, M., Akinwunmi, P., Flanagan, K. L., Lee, E. A. M., Doherty, T., Milligan, P., Jaye, A., Tornieporth, N., Ballou, R., Mcadam, K. P. M. J., Cohen, J., & Hill, A. V. S. (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), 286-293. https://doi.org/10.1111/j.1365-2249.2004.02371.x