Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/1109
Title: CD8 T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice.
Authors: Gupta, Nimesh
Agrawal, Mona
Kalia, Anurag
Keywords: Correlates-of-protection; Flavivirus vaccine; Japanese encephalitis; Neutralizing antibody; Tfh cells.
Issue Date: Aug-2020
Publisher: Wiley-VCH GmbH
Abstract: The live attenuated SA14-14-2 Japanese encephalitis (JE) vaccine is a historical vaccine that protects against JE. Despite its extensive use, the mechanism of protective immunity conferred by the SA14-14-2 vaccine is not well established. Here, we used mouse models to understand the mechanism of the development of humoral immunity against the vaccine. The vaccine induces robust GC responses within a week postimmunization. In lethal virus challenge, we show that CD4+ T cells alone, but not CD8+ T cells, are sufficient to confer vaccine-mediated protection. However, the CD4-mediated protection was potentiated in the presence of vaccine-primed CD8+ T cells. Employing CD8-deficient mice, we show that both the protective traits of CD4+ T cells and the quality of antibody response to the vaccine are impaired in absence of CD8+ T cells. We further demonstrate that the poor protective immune response induced by the vaccine in absence of CD8+ T cells is mainly due to the impaired differentiation and function of follicular Th cells, leading to suboptimal GC reaction. Our study highlights an unprecedented role of CD8+ T cells in the establishment of humoral responses to the vaccine. By elucidating underlying cellular determinants of vaccine-induced protective immunity, our work has implications for rational design of vaccines against JE virus and related flaviviruses.
URI: http://hdl.handle.net/123456789/1109
Appears in Collections:Vaccine Immunology Publications
Vaccine Immunology Publications
Vaccine Immunology Publications
Vaccine Immunology Publications

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