Ex vivo interferon-gamma immune response to thrombospondin-related adhesive protein in coastal Kenyans: longevity and risk of Plasmodium falciparum infection.
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.
Flanagan
Katie L
KL
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom. katie.flanagan@lshtm.ac.uk
Mwangi
Tabitha
T
Plebanski
Magdalena
M
Odhiambo
Kennedy
K
Ross
Amanda
A
Sheu
Eric
E
Kortok
Moses
M
Lowe
Brett
B
Marsh
Kevin
K
Hill
Adrian V S
AV
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
D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma