Title |
RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial
|
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Published in |
Frontiers in immunology, August 2017
|
DOI | 10.3389/fimmu.2017.01008 |
Pubmed ID | |
Authors |
Gemma Moncunill, Stephen C. De Rosa, Aintzane Ayestaran, Augusto J. Nhabomba, Maximillian Mpina, Kristen W. Cohen, Chenjerai Jairoce, Tobias Rutishauser, Joseph J. Campo, Jaroslaw Harezlak, Héctor Sanz, Núria Díez-Padrisa, Nana Aba Williams, Daryl Morris, John J. Aponte, Clarissa Valim, Claudia Daubenberger, Carlota Dobaño, M. Juliana McElrath |
Abstract |
Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4(+) T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4(+) T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4(+) T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4(+) T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4(+) T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies. |
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Mendeley readers
Geographical breakdown
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Student > Ph. D. Student | 15 | 15% |
Researcher | 15 | 15% |
Student > Master | 9 | 9% |
Student > Doctoral Student | 7 | 7% |
Student > Bachelor | 5 | 5% |
Other | 16 | 16% |
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Social Sciences | 3 | 3% |
Other | 11 | 11% |
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