title: A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.
abstract: 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.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: William H H
authors.initials: WH
authors.lastname: Reece
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Philip K
authors.initials: PK
authors.lastname: Gothard
authors.forename: Paul
authors.initials: P
authors.lastname: Milligan
authors.forename: Kalifa
authors.initials: K
authors.lastname: Bojang
authors.forename: Tom
authors.initials: T
authors.lastname: Doherty
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Peter
authors.initials: P
authors.lastname: Akinwunmi
authors.forename: Simone
authors.initials: S
authors.lastname: Everaere
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Watkins
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Nadia
authors.initials: N
authors.lastname: Tornieporth
authors.forename: Ali
authors.initials: A
authors.lastname: Alloueche
authors.forename: Brian M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Keith P W J
authors.initials: KP
authors.lastname: McAdam
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017124:Conserved Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008875:Middle Aged; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan