Moncunill, GemmaDe Rosa, Stephen C.Ayestaran, AintzaneNhabomba, Augusto J.Mpina, MaximillianCohen, Kristen W.Jairoce, ChenjeraiRutishauser, TobiasCampo, Joseph J.Harezlak, JaroslawSanz, HéctorDíez-Padrisa, NúriaWilliams, Nana AbaMorris, DarylAponte, John J.Valim, ClarissaDaubenberger, ClaudiaDobaño, CarlotaMcElrath, M. Juliana2017-12-052017Moncunill, G., S. C. De Rosa, A. Ayestaran, A. J. Nhabomba, M. Mpina, K. W. Cohen, C. Jairoce, et al. 2017. “RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial.” Frontiers in Immunology 8 (1): 1008. doi:10.3389/fimmu.2017.01008. http://dx.doi.org/10.3389/fimmu.2017.01008.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492105Comprehensive 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.en-USmalariavaccinecellular immune responsesT cellsintracellular cytokine stainingflow cytometryJournal Article2017-12-0510.3389/fimmu.2017.01008