First Author | Kalia A | Year | 2021 |
Journal | Eur J Immunol | Volume | 51 |
Issue | 2 | Pages | 368-379 |
PubMed ID | 32749679 | Mgi Jnum | J:302288 |
Mgi Id | MGI:6506954 | Doi | 10.1002/eji.202048745 |
Citation | Kalia A, et al. (2021) CD8(+) T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice. Eur J Immunol 51(2):368-379 |
abstractText | 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. |