RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial

Autor: 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
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Frontiers in Immunology, Vol 8 (2017)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2017.01008
Popis: 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.
Databáze: Directory of Open Access Journals