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Malaria vaccines based on thrombospondin-related adhesive protein of Plasmodium falciparum (Pf TRAP) are currently undergoing clinical trials in humans. This study was designed to investigate naturally acquired cellular immunity to Pf TRAP in adults from a target population for future trials of TRAP-based vaccines in Kilifi, Kenya. We first tested reactivity to a panel of 53 peptides spanning Pf TRAP and identified 26 novel T-cell epitopes. A panel of naturally occurring polymorphic variant epitope peptides were made to the most commonly recognized epitope regions and tested for ability to elicit IFN-
, IL-4, and IL-10 production. These data provide for the first time a complex cytokine matrix mapping naturally induced T-cell responses to TRAP and suggest that T-cell responses boosted by vaccination with Pf TRAP could stimulate the release of competing pro- and anti-inflammatory cytokines. They further define polymorphic variants able to boost specific Th1, Th2, and possibly Tr1 reactivity.
Received February 9, 2005. Accepted for publication July 9, 2005.
Acknowledgments: We would like to thank all the donors and field workers in Kilifi. The study was approved by The Kenya Medical Research Institute national ethical and scientific review committees and is published with the permission of the director of KEMRI. We would like to thank Felicity May and Martin Williams for technical assistance with TRAP typing and HLA typing, respectively.
Financial support: K.L.F. was funded by a Wellcome Trust Tropical Training Fellowship, K.J.R. is funded by the Medical Research Council, K.M. is funded by a Wellcome Trust Career Post in Tropical Medicine, and A.V.S.H. is a Wellcome Trust Principal Fellow.
* Address correspondence to Katie L. Flanagan, MRC Laboratories, P.O. Box 273, Fajara, The Gambia. E-mail: kflanagan{at}mrc.gm
Authors’ addresses: Katie L. Flanagan, MRC Laboratories, P.O. Box 273, Fajara, The Gambia, Telephone: +220-4495442, Fax: +220-4495919, E-mail: kflanagan{at}mrc.gm. Magdalena Plebanski, Austin Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia, Telehone: +61-3-92870643, Fax: +61-3-92870601. Kennedy Odhiambo, Tabitha Mwangi, Moses Kortok, Brett Lowe, and Kevin Marsh, KEMRI Centre for Geographic Medicine—Coast, P.O. Box 230, Kilifi, Kenya, Telephone: +254-1255-22390, Fax: +254-1255-22063. Eric Sheu, Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, 260 Longwood Avenue, Boston, MA 02115, Telephone: +1-617-432-1738, Fax: +1-617-432-0232. Colin Gelder and Keith Hart, Tenovus Building, University of Wales College of Medicine, Heath Park, Cardiff, UK, Telephone: +44(0)-29 20, Fax: +44(0)-29 20. Kathryn J. Robson, MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford, UK, Telephone: +44-(0)1865-222379, Fax: +44(0)-1865-222500. Adrian V. S. Hill, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK, Telephone: +44-(0)1865-287759, Fax: +44-(0)1865-287686.
Reprint requests: Katie L. Flanagan, MRC Laboratories, P.O. Box 273, Fajara, The Gambia, Telephone: +220-4495442, Fax: +220-4495919, E-mail: kflanagan{at}mrc.gm.
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