A Statistical Interaction between Circumsporozoite Protein-Specific T Cell and Antibody Responses and Risk of Clinical Malaria Episodes following Vaccination with RTS,S/AS01E |
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| Authors: | Francis M. Ndungu Jedidah Mwacharo Domtila Kimani Oscar Kai Philippe Moris Erik Jongert Johan Vekemans Ally Olotu Philip Bejon |
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| Affiliation: | 1. Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya.; 2. Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.; 3. GlaxoSmithKline Biologicals, Wavre, Belgium.; 4. Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom.; Université Pierre et Marie Curie, France, |
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| Abstract: | The candidate malaria vaccine RTS,S/AS01E provides significant but partial protection from clinical malaria. On in vitro circumsporozoite protein (CSP) peptide stimulation and intra-cellular cytokine staining of whole blood taken from 407 5–17 month-old children in a phase IIb trial of RTS,S/AS01E, we identified significantly increased frequencies of two CSP-specific CD4+ T cells phenotypes among RTS,S/AS01E vaccinees (IFNγ-IL2+TNF− and IFNγ-IL2+TNF+ CD4+ T cells), and increased frequency of IFNγ-IL2-TNF+ CD4+ T cells after natural exposure. All these T cells phenotypes were individually associated with reductions in the risk of clinical malaria, but IFNγ-IL2-TNF+ CD4+ T cells independently predicted reduced risk of clinical malaria on multi-variable analysis (HR = 0.29, 95% confidence intervals 0.15–0.54, p<0.0005). Furthermore, there was a strongly significant synergistic interaction between CSP-specific IFNγ-IL2-TNF+ CD4+ T cells and anti-CSP antibodies in determining protection against clinical malaria (p = 0.002). Vaccination strategies that combine potent cellular and antibody responses may enhance protection against malaria. |
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