A CD4(+) T-cell Immune Response to a Conserved Epitope in the Circumsporozoite Protein Correlates With Protection From Natural Plasmodium Falciparum Infection and Disease

Nat Med. 2004 Apr;10(4):406-10. doi: 10.1038/nm1009. Epub 2004 Mar 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Epitopes
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan