Title:
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RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T
Cell Responses in a Pediatric African Phase III Trial
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Author:
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Moncunill, Gemma; Rosa, Stephen C. de; Ayestaran, Aintzane; Nhabomba, Augusto; Mpina, Maximillian; Cohen, Kristen W.; Jairoce, Chenjerai; Rutishauser, Tobias; Campo, Joseph J.; Harezlak, Jaroslaw; Sanz, Héctor; Díez-Padrisa, Núria; Williams, Nana A.; Morris, Daryl; Aponte, John J.; Valim, Clarissa; Daubenberger, Claudia; Dobaño, Carlota, 1969-; McElrath, M.Juliana
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Abstract:
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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-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. |
Subject(s):
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-Malària -Plasmodium falciparum -Àfrica -Malaria -Plasmodium falciparum -Africa |
Rights:
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cc by (c) Moncunill et al. , 2017
http://creativecommons.org/licenses/by/4.0/ |
Document type:
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Article Article - Published version |
Published by:
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Frontiers Media
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