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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 infection1. 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-γ-secreting CD4+ T cells specific for a conserved sequence from the circumsporozoite protein, which binds to many human leukocyte antigen (HLA)-DR types2. 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 cells3,4. 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.

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Figure 1: Cultured ELISPOT response to peptide 22, measured at start of malaria season (2 weeks after vaccine dose 3), correlates with time to parasitemia in pooled cohorts.
Figure 2: T-cell immune responses.


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We thank the volunteers who participated in this study; the malaria field and laboratory staff, the Local Safety Monitor (T. Corrah), the Data Safety Monitoring Committee (chair, P. Smith); the WHO Independent Monitors (M. Molyneux and F. Binka); and C. Holland and H. Whittle for help and advice. A.V.S.H. is a Wellcome Trust Principal Research Fellow. This study was supported by an EC Demonstration Project Grant (PL962164) and by the Wellcome Trust.

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Correspondence to Adrian V S Hill.

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A.V.S.H. is a consultant to and cofounder of Oxxon Pharmaccines Ltd., Oxford, UK. G.V., N.T. and J.C. are employees of GlaxoSmithKline Biologicals, Rixensart, Belgium.

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Reece, W., Pinder, M., Gothard, P. et al. 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 10, 406–410 (2004).

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