A viral vector-based vaccine to induce humoral and cellular immune protection against Powassan virus in a tick transmission model

ABSTRACT We aim to develop a safe and effective vaccine that provides robust protection against Powassan virus (POWV). Our working hypothesis is that the safe and effective induction of both branches of the adaptive immune response are critical to counteract Flavivirus infections such as POWV; this includes the humoral (neutralizing antibody) response that prevents virus dissemination into the host, and T cell mediated responses that appear to be required for early containment of the pathogen. Accordingly, our vaccine design is based on the modified vaccinia Ankara vector (MVA), a vaccine platform used in humans that is well characterized for its safety and the stimulation of both humoral and cellular immune responses. Our vaccine design incorporates the surface proteins E and prM that are known to induce neutralizing antibodies as a prM-E construct, and adds the non-structural 1 protein (NSl), known to activate the host cellular immune mechanisms against the Flaviviridae family. Using this vaccine design, we will test the hypothesis that simultaneous engagement of the humoral and cellular immune mechanisms provides optimal protection from POWV infection in mice.