Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination
E. Taylor Stone, Mariah Hassert, Elizabeth Geerling, Colleen Wagner, James D. Brien, Gregory D. Ebel, Alec J. Hirsch, Cody N. German, Jessica L. Smith, Amelia K. Pinto
Abstract
Powassan virus (POWV) is a tick-borne pathogen for which humans are an incidental host. POWV infection can be fatal or result in long-term neurological sequelae; however, there are no approved vaccinations for POWV. Integral to efficacious vaccine development is the identification of correlates of protection, which we accomplished in this study by utilizing a murine model of POWV infection. Using POWV lethal and sub-lethal challenge models, we show that (1) robust B and T cell responses are necessary for immune protection, (2) POWV lethality can be attributed to both viral- and host-mediated drivers of disease, and (3) knowledge of the immune correlates of protection against POWV can be applied in a virus-like particle (VLP)-based vaccination approach that provides protection from lethal POWV challenge. Identification of these immune protection factors is significant as it will aid in the rational design of POWV vaccines.