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

L2 Diagnostics LLC received a $281,786 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) awarded on September 23, 2025, with completion scheduled for August 31, 2027. The company will develop a viral vector-based vaccine against Powassan virus (POWV), a tick-borne pathogen in the Flavivirus family. The vaccine platform utilizes Modified Vaccinia Ankara (MVA), an established vaccine vector, incorporating surface proteins E and PRM that induce neutralizing antibodies, combined with non-structural protein 1 (NS1) to activate cellular immune responses. This dual-mechanism approach aims to provide comprehensive protection by simultaneously engaging both humoral and cellular adaptive immune responses.

The project will evaluate vaccine efficacy through testing in a mouse infection model to validate the hypothesis that coordinated activation of both immune branches provides optimal protection against POWV infection. Research will be conducted at the awardee's facility in Woodbridge, Connecticut. This award aligns with NIAID's strategic priority of supporting innovative vaccine development and translational research addressing emerging infectious disease threats, particularly those transmitted by arthropod vectors.

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.