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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.

Original publication




Journal article


Nat Med

Publication Date





406 - 410


Adolescent, Adult, Amino Acid Sequence, CD4-Positive T-Lymphocytes, Conserved Sequence, Enzyme-Linked Immunosorbent Assay, Epitopes, Humans, Immunologic Memory, Malaria, Falciparum, Middle Aged, Molecular Sequence Data, Protozoan Proteins