Development of a Powassan virus-like particle vaccine adjuvanted with novel Toll-like receptor agonists

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B184
Abstract ID: 5190

Presenting Author:
Michael W Crawford , Graduate Student at Oregon Hlth. & Sci.Univ.

Abstract:

Powassan virus (POWV) is an emerging tick-borne virus of the Flavivirus genus that can lead to serious neuroinvasive disease with a 10% case fatality rate. Although the number of people infected per year is relatively low, the range of the vector (Ixodes scapularis) that transmits POWV is expanding within North America, and the number of infections is rising. There are currently no vaccines. Research in our lab is focused on development of flavivirus-targeting virus like particle (VLP) vaccines. Previous work has demonstrated that a VLP vaccination strategy is highly effective at preventing Zika virus (ZIKV) infection in murine and nonhuman primate (NHP) models.  We have adapted this strategy to target POWV and are characterizing the immune responses and efficacy of VLPs when paired with several novel adjuvants in mice. The University of Montana component of our team has patented a novel lipidated TLR7/8 agonist and a novel TLR4 agonist which have demonstrated the ability to skew the immune response towards Th1 and Th1/Th2, respectively. We have demonstrated that POW-VLPs when combined with these agonists induce significantly higher levels of POWV-binding and neutralizing antibodies than VLP alone or with Alum. Furthermore, adjuvanted VLP vaccination results in complete protection against POWV challenge in a murine model. Current studies are focused on exploring the role of neutralizing antibody versus cell-mediated immunity in this protection.