A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.
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.
Reece
William H H
WH
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Pinder
Margaret
M
Gothard
Philip K
PK
Milligan
Paul
P
Bojang
Kalifa
K
Doherty
Tom
T
Plebanski
Magdalena
M
Akinwunmi
Peter
P
Everaere
Simone
S
Watkins
Katherine R
KR
Voss
Gerald
G
Tornieporth
Nadia
N
Alloueche
Ali
A
Greenwood
Brian M
BM
Kester
Kent E
KE
McAdam
Keith P W J
KP
Cohen
Joe
J
Hill
Adrian V S
AV
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*
D000939:Epitopes; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan