| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
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.
This article has been cited by other articles:
|
|
 |
|
  S. Sridhar, A. Reyes-Sandoval, S. J. Draper, A. C. Moore, S. C. Gilbert, G. P. Gao, J. M. Wilson, and A. V. S. Hill Single-Dose Protection against Plasmodium berghei by a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron A J. Virol., April 15, 2008; 82(8): 3822 - 3833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bejon, J. Mwacharo, O. Kai, S. Todryk, S. Keating, B. Lowe, T. Lang, T. W. Mwangi, S. C. Gilbert, N. Peshu, et al. The Induction and Persistence of T Cell IFN-{gamma} Responses after Vaccination or Natural Exposure Is Suppressed by Plasmodium falciparum J. Immunol., September 15, 2007; 179(6): 4193 - 4201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Garcia, A. Puentes, and M. E. Patarroyo Developmental Biology of Sporozoite-Host Interactions in Plasmodium falciparum Malaria: Implications for Vaccine Design Clin. Microbiol. Rev., October 1, 2006; 19(4): 686 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Dunachie, M. Walther, J. E. Epstein, S. Keating, T. Berthoud, L. Andrews, R. F. Andersen, P. Bejon, N. Goonetilleke, I. Poulton, et al. A DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccine Encoding Thrombospondin-Related Adhesion Protein but Not Circumsporozoite Protein Partially Protects Healthy Malaria-Naive Adults against Plasmodium falciparum Sporozoite Challenge. Infect. Immun., October 1, 2006; 74(10): 5933 - 5942. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. MOORMANN, C. C. JOHN, P. O. SUMBA, D. TISCH, P. EMBURY, and J. W. KAZURA STABILITY OF INTERFERON-{gamma} AND INTERLEUKIN-10 RESPONSES TO PLASMODIUM FALCIPARUM LIVER STAGE ANTIGEN-1 AND THROMBOSPONDIN-RELATED ADHESIVE PROTEIN IN RESIDENTS OF A MALARIA HOLOENDEMIC AREA Am J Trop Med Hyg, April 1, 2006; 74(4): 585 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. FLANAGAN, M. PLEBANSKI, K. ODHIAMBO, E. SHEU, T. MWANGI, C. GELDER, K. HART, M. KORTOK, B. LOWE, K. J. ROBSON, et al. CELLULAR REACTIVITY TO THE P. FALCIPARUM PROTEIN TRAP IN ADULT KENYANS: NOVEL EPITOPES, COMPLEX CYTOKINE PATTERNS, AND THE IMPACT OF NATURAL ANTIGENIC VARIATION. Am J Trop Med Hyg, March 1, 2006; 74(3): 367 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Lyke, R. B. Burges, Y. Cissoko, L. Sangare, A. Kone, M. Dao, I. Diarra, M. A. Fernandez-Vina, C. V. Plowe, O. K. Doumbo, et al. HLA-A2 Supertype-Restricted Cell-Mediated Immunity by Peripheral Blood Mononuclear Cells Derived from Malian Children with Severe or Uncomplicated Plasmodium falciparum Malaria and Healthy Controls Infect. Immun., September 1, 2005; 73(9): 5799 - 5808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. John, A. M. Moormann, P. O. Sumba, A. V. Ofulla, D. C. Pregibon, and J. W. Kazura Gamma Interferon Responses to Plasmodium falciparum Liver-Stage Antigen 1 and Thrombospondin-Related Adhesive Protein and Their Relationship to Age, Transmission Intensity, and Protection against Malaria Infect. Immun., September 1, 2004; 72(9): 5135 - 5142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Okhuysen, G. A. Rogers, A. Crisanti, F. Spano, D. B. Huang, C. L. Chappell, and S. Tzipori Antibody Response of Healthy Adults to Recombinant Thrombospondin-Related Adhesive Protein of Cryptosporidium 1 after Experimental Exposure to Cryptosporidium Oocysts Clin. Vaccine Immunol., March 1, 2004; 11(2): 235 - 238. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
