CD8+ T cells are crucial for humoral immunity establishment by SA14-14-2 live attenuated Japanese encephalitis vaccine in mice

Eur J Immunol. 2021 Feb;51(2):368-379. doi: 10.1002/eji.202048745. Epub 2020 Aug 19.


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.

Keywords: Correlates-of-protection; Flavivirus vaccine; Japanese encephalitis; Neutralizing antibody; Tfh cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Encephalitis Virus, Japanese / immunology*
  • Encephalitis, Japanese / immunology*
  • Immunity, Humoral / immunology*
  • Japanese Encephalitis Vaccines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Vaccination / methods
  • Vaccines, Attenuated / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Japanese Encephalitis Vaccines
  • Vaccines, Attenuated