title: Ex vivo interferon-gamma immune response to thrombospondin-related adhesive protein in coastal Kenyans: longevity and risk of Plasmodium falciparum infection.
abstract: Thrombospondin-related adhesive protein (TRAP) of Plasmodium falciparum is currently being tested in human vaccine studies. However, its natural reactivity in the field remains poorly characterized. More than 40% of 217 Kenyan donors responded in an ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay to at least one of 14 20mer peptides spanning 42% of the antigen. Reactivity was comparable from early childhood (>1 year of age) to old age, and the maximal precursor frequency of TRAP-specific cells to all 14 peptides was 1 in 4,000. Prospective follow-up for one year indicated that these low-level ex vivo responses to TRAP did not protect against the subsequent development of malaria. Retesting of selected donors after one year showed a complete change in the reactivity pattern, suggesting that malaria-specific ex vivo IFN-gamma ELISPOT assay responses are short lived in naturally exposed donors, even to conserved epitopes. This study provides important information regarding natural reactivity to a key malaria antigen.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom. katie.flanagan@lshtm.ac.uk
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: Tabitha
authors.initials: T
authors.lastname: Mwangi
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Kennedy
authors.initials: K
authors.lastname: Odhiambo
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.forename: Eric
authors.initials: E
authors.lastname: Sheu
authors.forename: Moses
authors.initials: M
authors.lastname: Kortok
authors.forename: Brett
authors.initials: B
authors.lastname: Lowe
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000737:chemistry; D007630:Kenya / Q000453:epidemiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008136:Longevity; D017780:Malaria Vaccines / Q000592:standards*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010865:Pilot Projects; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma