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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.

Abstract
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.
AuthorsKatie L Flanagan, Tabitha Mwangi, Magdalena Plebanski, Kennedy Odhiambo, Amanda Ross, Eric Sheu, Moses Kortok, Brett Lowe, Kevin Marsh, Adrian V S Hill
JournalThe American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 68 Issue 4 Pg. 421-30 (Apr 2003) ISSN: 0002-9637 [Print] United States
PMID12875291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Malaria Vaccines
  • Peptide Fragments
  • Protozoan Proteins
  • thrombospondin-related adhesive protein, protozoan
  • Interferon-gamma
Topics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunity, Cellular
  • Infant
  • Interferon-gamma (biosynthesis, chemistry)
  • Kenya (epidemiology)
  • Leukocytes, Mononuclear (immunology)
  • Longevity
  • Malaria Vaccines (standards)
  • Malaria, Falciparum (epidemiology, immunology, prevention & control)
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments (immunology)
  • Pilot Projects
  • Protozoan Proteins (chemistry, immunology)
  • Risk Factors
  • T-Lymphocytes (immunology)

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