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

• Published in: The American journal of tropical medicine and hygiene Vol. 68; no. 4; pp. 421 - 430
• Main Authors: FLANAGAN, KATIE L, MWANGI, TABITHA, PLEBANSKI, MAGDALENA, ODHIAMBO, KENNEDY, ROSS, AMANDA, SHEU, ERIC, KORTOK, MOSES, LOWE, BRETT, MARSH, KEVIN, HILL, ADRIAN V. S
• Format: Journal Article
• Language: English
• Published: Lawrence, KS ASTMH 01.04.2003; Allen Press
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Biological and medical sciences; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Human protozoal diseases; Humans; Immunity, Cellular; Infant; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - chemistry; Kenya - epidemiology; Leukocytes, Mononuclear - immunology; Longevity; Malaria; Malaria Vaccines - standards; Malaria, Falciparum - epidemiology; Malaria, Falciparum - immunology; Malaria, Falciparum - prevention & control; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Parasitic diseases; Peptide Fragments - immunology; Pilot Projects; Protozoal diseases; Protozoan Proteins - chemistry; Protozoan Proteins - immunology; Risk Factors; T-Lymphocytes - immunology; Tropical medicine; Kenya; Africa; Human; Protozoa; Apicomplexa; Protozoal disease; Immune response; Malaria; Parasitosis; Longevity; Protein; Infection; Plasmodium falciparum; Ex vivo; Risk factor; Gamma interferon; Thrombospondin
• ISSN: 0002-9637; 1476-1645
• DOI: 10.4269/ajtmh.2003.68.421

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.