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.
Original language | English |
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Article number | 110388 |
Journal | Cell Reports |
Volume | 38 |
Issue number | 7 |
DOIs | |
State | Published - Feb 15 2022 |
Bibliographical note
Publisher Copyright:© 2022 The Authors
Funding
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 , and in part by the Department of Defense (award no. PR192269 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funders | Funder number |
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National Institutes of Health (NIH) | |
U.S. Department of Defense | PR192269 |
National Institute of Allergy and Infectious Diseases | 5R01AI137424-03, R01AI152192, F31AI152460-01 |
Keywords
- Adaptive immunity
- arthropod-borne virus
- deer-tick virus
- immune protection
- murine model
- powassan virus
- tick-borne flavivirus
- tick-borne pathogens
- virus-like particle
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology