Cytotoxic T lymphocyte (CTL) low-responsiveness to the Plasmodium falciparum circumsporozoite protein in naturally-exposed endemic populations: analysis of human CTL response to most known variants

Doolan, Denise L., Khamboonruang, Chirasak, Beck, Hans-Peter, Houghten, Richard A., and Good, Michael F. (1993) Cytotoxic T lymphocyte (CTL) low-responsiveness to the Plasmodium falciparum circumsporozoite protein in naturally-exposed endemic populations: analysis of human CTL response to most known variants. International Immunology, 5 (1). pp. 37-46.

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Abstract

Cytotoxic T lymphocytes (CTL) specific for epitope(s) within the circumsporozoite (CS) protein of malaria sporozoites have been shown to play an important role in protective immunity against malaria, at least in murine models. Their role in sporozoite immunity in the human host has, however, not yet been elucidated. Immunological non-responsiveness and antigenlc diversity within T cell epitopes of the CS protein have been identified as potential problems in producing a sporozoite vaccine. These factors may contribute to the widespread lack of sporozoite immunity in endemic populations. In this study, 137 individuals with a history of natural endemic exposure to falciparum sporozoites (119 resident in north west Thailand and 18 resident in coastal Papua New Guinea) were tested for a CTL response to the Plasmodium falciparum CS protein Fifty-four overlapping peptides, spanning the entire sequence of the CS protein of P. falciparum including most known variants, were studied. While most individuals had antibodies to the immunodominant B cell repeat, (NANP)ₙ, and while CTL specific for an influenza virus matrix synthetic peptide could be generated from five of 23 Karen Thai individuals tested, no CS protein-specific CTL could be detected in these populations. Our data have important implications for vaccine programs.

Item ID: 42785
Item Type: Article (Refereed Research - C1)
Keywords: malaria vaccines; sporozoite immunity
ISSN: 1460-2377
Funders: National Health and Medical Research Council (NHMRC), Queensland Institute of Medical Research Tropical Health Program (QIMRTHP)
Date Deposited: 21 Mar 2016 04:56
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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