γδ T Cells Mediate Protective Immunity Following Vaccination with an Insect-Based Chikungunya Fever Vaccine in Mice

Eilat (EILV)/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that γδ T cells contribute to EILV/CHIKV-induced host protection against WT CHIKV infection. TCRδ^−/− mice, which are deficient of γδ T cells, had impaired CHIKV-specific CD8⁺ T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8⁺ T cells of EILV/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, γδ T cells expanded quickly in response to EILV/CHIKV vaccination. TCRδ^−/− mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, γδ T cells contribute to EILV/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV/CHIKV vaccination.