Open AccessA Statistical Interaction between Circumsporozoite Protein-Specific T Cell and Antibody Responses and Risk of Clinical Malaria Episodes following Vaccination with RTS,S/AS01E
Author(s) -
Francis M. Ndungu,
Jedidah Mwacharo,
Domtila Kimani,
Oscar Kai,
Philippe Moris,
Erik Jongert,
Johan Vekemans,
Ally Olotu,
Philip Bejon
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0052870
Subject(s) - circumsporozoite protein , malaria , malaria vaccine , immunology , vaccination , antibody , immune system , virology , plasmodium falciparum , medicine , cytokine , tumor necrosis factor alpha , t cell , biology
The candidate malaria vaccine RTS,S/AS01 E 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/AS01 E , we identified significantly increased frequencies of two CSP-specific CD4+ T cells phenotypes among RTS,S/AS01 E 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.