A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.
Reece, William HH;
Pinder, Margaret;
Gothard, Philip K;
Milligan, Paul;
Bojang, Kalifa;
Doherty, Tom;
Plebanski, Magdalena;
Akinwunmi, Peter;
Everaere, Simone;
Watkins, Katherine R;
+8 more...Voss, Gerald;
Tornieporth, Nadia;
Alloueche, Ali;
Greenwood, Brian M;
Kester, Kent E;
McAdam, Keith PWJ;
Cohen, Joe;
Hill, Adrian VS;
(2004)
A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.
Nature medicine, 10 (4).
pp. 406-410.
ISSN 1078-8956
DOI: https://doi.org/10.1038/nm1009
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Many human T-cell responses specific for epitopes in Plasmodium falciparum have been described, but none has yet been shown to be predictive of protection against natural malaria infection. Here we report a peptide-specific T-cell assay that is strongly associated with protection of humans in The Gambia, West Africa, from both malaria infection and disease. The assay detects interferon-gamma-secreting CD4(+) T cells specific for a conserved sequence from the circumsporozoite protein, which binds to many human leukocyte antigen (HLA)-DR types. The correlation was observed using a cultured, rather than an ex vivo, ELISPOT assay that measures central memory-'type T cells rather than activated effector T cells. These findings provide direct evidence for a protective role for CD4(+) T cells in humans, and a precise target for the design of improved vaccines against P. falciparum.