Abstract |
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.
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Authors | Francis M Ndungu, Jedidah Mwacharo, Domtila Kimani, Oscar Kai, Philippe Moris, Erik Jongert, Johan Vekemans, Ally Olotu, Philip Bejon |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 12
Pg. e52870
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23300801
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Protozoan
- Cytokines
- Malaria Vaccines
- Protozoan Proteins
- RTS,S-AS01E vaccine
- circumsporozoite protein, Protozoan
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Topics |
- Antibodies, Protozoan
(blood)
- Antibody Formation
- CD4-Positive T-Lymphocytes
(immunology, metabolism)
- CD8-Positive T-Lymphocytes
(immunology, metabolism)
- Clinical Trials, Phase II as Topic
- Cytokines
(blood)
- Humans
- Infant
- Kaplan-Meier Estimate
- Malaria Vaccines
- Malaria, Falciparum
(blood, immunology, prevention & control)
- Plasmodium falciparum
(immunology)
- Proportional Hazards Models
- Protozoan Proteins
(immunology, metabolism)
- Randomized Controlled Trials as Topic
- Risk
- Sporozoites
(immunology)
- Vaccination
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