Upper respiratory tract resident memory CD8 T cells limit viral transmission and provide durable protection.

Abstract

Abstract An effective vaccine against respiratory viruses should not only limit disease in infected individuals, but also restrain viral dissemination among the population. Furthermore, directing vaccine responses to conserved viral epitopes can offer cross-strain protection and potentially limit viral escape from pre-existing immunity. Although studies have demonstrated that intranasal vaccination can generate populations of resident memory CD8 T cells (T RM) throughout the respiratory tract that can rapidly clear a secondary infection and limit immunopathology, the ability of CD8 T RMto limit natural respiratory virus transmission has not yet been evaluated. To address this gap in knowledge, we developed a model of parainfluenza virus transmission whereby a bioluminescent Sendai virus can be used in conjunction with in vivo imaging to track transmission dynamics longitudinally across murine cohorts. Recombinant influenza and adenoviral vectors expressing the immunodominant Sendai virus nucleoprotein CD8 T cell epitope enable the establishment of Sendai virus-specific CD8 T RMthroughout the respiratory tract without inducing Sendai-specific antibodies. Using these models, we demonstrate that virus-specific CD8 T RMcan inhibit the establishment of infection in immunized hosts and prevent respiratory virus transmission. Additionally, we show that protection against respiratory virus transmission is mediated through T RMlocalized in the upper respiratory tract and is durable for at least six months. These results indicate that vaccines which induce localized T cell immunity at the initial site of respiratory virus infection can contribute to the generation of herd immunity and limit viral spread in the population. This project is supported by NIH grants R35 HL150803 and U01 HL139483.