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

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.

Protective Immune Responses Induced by an mRNA-LNP Vaccine Encoding prM-E Proteins against Japanese Encephalitis Virus Infection

“…In this study, immunization of the attenuated vaccine enhanced the CD4 + T cell responses significantly (Figure 2C), which may explain the high titer of neutralizing antibodies detected in the SA14-14-2 group. This finding is consistent with a previous study which reported that the CD4 + T cells stimulated by the SA14-14-2-attenuated vaccine are sufficient to give complete protection to mice, depending on the antibody response [35]. It has been well known that an mRNA vaccine could stimulate both CD4 + and CD8 + T cell responses [36].…”

NK- and T-cell granzyme B and K expression correlates with age, CMV infection and influenza vaccine-induced antibody titres in older adults

“…Although NK- and CD8 + T-cells are most often associated with the cytolytic response to respiratory infection, previous studies suggest that they are also important for vaccine-induced antibody responses to antigens from influenza ( Herrero-Fernández et al, 2019 ; Picard et al, 2022 ) and other pathogens ( Kalia et al, 2021 ). Given this, we sought to determine whether cell-specific granzyme expression was associated with hemagglutination inhibition (HAI) antibody titres prior to and following seasonal high-dose vaccination in our older adult participants.…”

The Japanese Encephalitis Antigenic Complex Viruses: From Structure to Immunity

“…On the other hand, CD8+ is essential for clearance of WNV and in the CNS and recovery in mouse models [ 162 ], and variation in susceptibility was observed in mice deficient in Fas- or perforin-dependent cytolytic pathways between WNV lineage I and II, JEV and MVEV [ 161 ], which highlights the importance of elucidating a T cell response for specific flaviviruses of the same antigenic complex. Recent studies highlighted the important role of CD8+ cells in eliciting antibody-mediated protection in response to JEV vaccination in mice and in protecting JEV-infected mice via granule-mediated cytotoxic effects with a contribution of γ/δ TCR expressing T cells [ 163 , 164 ]. The T cell immune response in MVEV and USUV infections is less thoroughly defined.…”