期刊
FRONTIERS IN IMMUNOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01008
关键词
malaria; Plasmodium falciparum; vaccine; cellular immune responses; T cells; intracellular cytokine staining; flow cytometry
类别
资金
- PATH Malaria Vaccine Initiative (MVI)
- National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) [R01AI095789]
- HIV Vaccine Trials Network Laboratory Center (HVTN, National Institute of Allergy and Infectious Diseases) [UM1 AI068618]
- Human Immunology Project Consortium (HIPC, National Institute of Allergy and Infectious Diseases) [P30 AI027757]
- Instituto de Salud Carlos III [PS11/00423]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca AGAUR [2014SGR991]
- Sara Borrell - ISCIII fellowship [CD010/00156]
- Ramon y Cajal Contract from the Ministerio de Economia y Competitividad [RYC-2008-02631]
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-alpha 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.
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