title: Plasmodium falciparum liver-stage antigen-1 peptide-specific interferon-gamma responses are not suppressed during uncomplicated malaria in African children.
abstract: Liver-stage antigen (LSA)-1 is a candidate vaccine molecule for Plasmodium falciparum malaria, but knowledge of the evolution of naturally acquired immune responses to LSA-1 in African children is lacking. We therefore assessed cellular immune responses to two defined T cell epitopes of LSA-1, during and after uncomplicated P. falciparum malaria in a group of Gabonese children. In terms of their prevalence, interferon (IFN)-gamma responses of peripheral blood mononuclear cells (PBMC) to an LSA-1 N-terminal peptide, T1, were significantly higher when measured during the acute phase compared with convalescence. IFN-gamma responses to the LSA-J (hinge region) peptide showed a similar profile, but at a lower prevalence. Depletion experiments confirmed that CD8+ T cells are a major source of peptide-driven IFN-gamma, but both lymphoproliferation and the production of IL-10 in response to either of the peptides was low in all children at all times. PBMC from 25% of the children failed to produce IFN-gamma in response to either peptide at any time-point. The results suggest that lymphocytes producing IFN-gamma in response to at least one T cell epitope of LSA-1 are most frequent in the peripheral circulation during the acute phase of P. falciparum malaria. Thus, in this case, the generalised suppression of cell-mediated responses which characterises acute malaria does not affect liver-stage antigen-specific IFN-gamma production. These findings imply that measurements of the frequency of parasite antigen-specific cellular immune responses in clinically healthy individuals may represent significant underestimations, which has important implications for the design of field-based vaccine antigen-related studies.
authors.affiliation: Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany. adrian.luty@uni-tuebingen.de
authors.forename: A J
authors.initials: AJ
authors.lastname: Luty
authors.forename: M
authors.initials: M
authors.lastname: Bongartz
authors.forename: P
authors.initials: P
authors.lastname: Rezbach
authors.forename: J F
authors.initials: JF
authors.lastname: Faucher
authors.forename: M R
authors.initials: MR
authors.lastname: Hollingdale
authors.forename: P G
authors.initials: PG
authors.lastname: Kremsner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis*; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; C067302:liver stage-specific antigen, Plasmodium; D007371:Interferon-gamma