γδ T cells mediate protective immune responses following an insect virus-based Chikungunya virus chimera vaccine

Abstract

Abstract Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes acute chikungunya fever (CHIKF) which often is accompanied by severe and persistent arthralgia. There are currently no licensed human vaccines against CHIKV. Eilat virus (EILV), a mosquito-specific alphavirus, replicates well in mosquito cells, but not in vertebrate cells. EILV/CHIKV is a chimeric CHIKV vaccine candidate that contains the nonstructural proteins of EILV and the structural proteins of CHIKV. This chimera vaccine candidate has been shown to protect against wild-type (WT) CHIKV challenge in mice and non-human primates (NHPs), yet the immune mechanism of the vaccine-induced host protection remains unknown. γδ T cells are known to react to WT CHIKV infection by controlling CHIKV inflammation, cell infiltration, and tissue damage. We found that γδ T cells are expanded following vaccination with EILV/CHIKV. TCRδ −/−mice, which are deficient of γδ T cells, exhibited a reduced CD8 +T cell effector function response at different timepoints compared to WT mice. This reduced CD8 +T cell response was also observed 7 days post WT CHIKV infection in the vaccinated mice. A significant reduction of CHIKV-specific IgM titers was also observed 7 days post WT CHIKV challenge in the vaccinated mice. Lastly, we noted that the vaccinated TCRδ −/−mice had higher levels of viremia than vaccinate WT mice following challenge with WT CHIKV. Overall, our results suggest that γδ T cells contribute to the host protection by promoting vaccine induced CD8 +T cell and antibody responses against CHIKV infection.