Moncunill Piñas, GemmaRosa, Stephen C. deAyestaran, AintzaneNhabomba, Augusto J.Mpina, MaximilianCohen, Kristen W.Jairoce, Chenjerai Tobias SixpenceRutishauser, TobiasCampo, Joseph J.Harezlak, JaroslawSanz Ródenas, HéctorDíez-Padrisa, NúriaWilliams, Nana AbaMorris, DarylAponte, John J.Valim, ClarissaDaubenberger, ClaudiaDobaño, Carlota, 1969-McElrath, M.Juliana2017-10-052017-10-052017-08-231664-3224https://hdl.handle.net/2445/116227Comprehensive 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-alpha, and CD40L and HBsAg-specific CD4+ T producing IFN-gamma 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.14 p.application/pdfengcc by (c) Moncunill et al. , 2017http://creativecommons.org/licenses/by/4.0/MalàriaPlasmodium falciparumÀfricaMalariaPlasmodium falciparumAfricainfo:eu-repo/semantics/article2017-10-04info:eu-repo/semantics/openAccess28878775