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EX VIVO INTERFERON-GAMMA IMMUNE RESPONSE TO THROMBOSPONDIN-RELATED ADHESIVE PROTEIN IN COASTAL KENYANS: LONGEVITY AND RISK OF PLASMODIUM FALCIPARUM INFECTION

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  • 1 Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom; KEMRI-Centre for Geographic Medicine-Coast, PO Box 230, Kilifi, Kenya
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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-γ (IFN-γ) 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-γ 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.

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