Cellular immunity induced by the recombinant Plasmodium falciparum malaria vaccine, RTS,S/AS02, in semi-immune adults in The Gambia
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 22, 2004
- Source ID
- 10.1111/j.1365-2249.2004.02371.x
Entities
People
- A Jaye
- A V S Hill
- E A M Lee
- Jonathan D. Cohen
- K L Flanagan
- K P M J Mcadam
- M Pinder
- M Plebanski
- N Tornieporth
- P Akinwunmi
- P Milligan
- R Ballou
- T. Doherty
- W H H Reece
Organizations
- Burnet Institute
- GSK
- John Radcliffe Hospital
- Medical Research Council
- Walter Reed Army Institute of Research