title: 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)-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.
authors.affiliation: Medical Research Council Laboratories, Banjul, The Gambia. mpinder@mrc.gm
authors.forename: M
authors.initials: M
authors.lastname: Pinder
authors.forename: W H H
authors.initials: WH
authors.lastname: Reece
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
authors.forename: P
authors.initials: P
authors.lastname: Akinwunmi
authors.forename: K L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: E A M
authors.initials: EA
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Doherty
authors.forename: P
authors.initials: P
authors.lastname: Milligan
authors.forename: A
authors.initials: A
authors.lastname: Jaye
authors.forename: N
authors.initials: N
authors.lastname: Tornieporth
authors.forename: R
authors.initials: R
authors.lastname: Ballou
authors.forename: K P M J
authors.initials: KP
authors.lastname: McAdam
authors.forename: J
authors.initials: J
authors.lastname: Cohen
authors.forename: A V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D015331:Cohort Studies; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005714:Gambia; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma