Requirement for robust T and B cell responses for immune protection against Powassan virus (POWV) in virus-like particle (VLP) vaccination.

Abstract

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 immune 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. We also provide evidence that POWV-experienced CD8+ T cells may potentiate immune-mediated pathogenesis during infection. Identification of beneficial and detrimental aspects of POWV-immune protection is significant as it will aid in the rational design of POWV vaccines. This research was supported in part by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID): 5R01AI152192-02, 5R01AI137424-03 and F31AI152460-01. This research was also supported in part by the Department of Defense (Award#: PR192269). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.