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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-
(IFN-) 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- 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.
Received September 30, 2002. Accepted for publication December 26, 2002.
Acknowledgments: We thank the residents of Ngerenya for participating in this study, and all the field staff involved in the longitudinal follow-up. Katie L. Flanagan was funded by a Wellcome Trust Clinical Tropical Training Fellowship. Magdalena Plebanski is a Howard Hughes Scholar. Adrian V. S. Hill and Kevin Marsh are Wellcome Trust Principal Fellows.
Authors’ addresses: Katie L. Flanagan, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom, Telephone: 44-208-864-3232, Fax: 44-208-869-2009, E-mail: katie.flanagan{at}lshtm.ac.uk. Tabitha Mwangi, Kennedy Odhiambo, Amanda Ross, Moses Kortok, Brett Lowe, and Kevin Marsh, KEMRI-Centre for Geographic Medicine-Coast, PO Box 230, Kilifi, Kenya. Magdalena Plebanski, Vaccine Development and Infectious Diseases Unit, The Austin Research Institute, The Austin and Repatriation Medical Centre, Studley Road, Heildelberg, Victoria 3084, Australia. Eric Sheu and Adrian V. S. Hill, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom.
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