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Front Immunol. 2017 Aug 23;8:1008. doi: 10.3389/fimmu.2017.01008. eCollection 2017.

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

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ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.
Ifakara Health Institute, Bagamoyo Research and Training Centre, Bagamoyo, Tanzania.
Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Department of Epidemiology and Biostatistics, School of Public Health-Bloomington, Indiana University, Bloomington, IN, United States.
Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, MI, United States.
Department of Immunology and Infectious Diseases, Harvard T.H. Chen School of Public Health, Boston, MA, United States.
Department of Medicine, University of Washington, Seattle, WA, United States.


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.


Plasmodium falciparum; T cells; cellular immune responses; flow cytometry; intracellular cytokine staining; malaria; vaccine

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