Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination

E. Taylor Stone; Mariah Hassert; Elizabeth Geerling; Colleen Wagner; James D. Brien; Gregory D. Ebel; Alec J. Hirsch; Cody German; Jessica L. Smith; Amelia K. Pinto

doi:10.1016/j.celrep.2022.110388

Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination

E. Taylor Stone, Mariah Hassert, Elizabeth Geerling, Colleen Wagner, James D. Brien, Gregory D. Ebel, Alec J. Hirsch, Cody German, Jessica L. Smith, Amelia K. Pinto

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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
Article number	110388
Journal	Cell Reports
Volume	38
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2022.110388
State	Published - Feb 15 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2022.110388

Cite this

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title = "Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination",

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.",

keywords = "Adaptive immunity, arthropod-borne virus, deer-tick virus, immune protection, murine model, powassan virus, tick-borne flavivirus, tick-borne pathogens, virus-like particle",

author = "Stone, {E. Taylor} and Mariah Hassert and Elizabeth Geerling and Colleen Wagner and Brien, {James D.} and Ebel, {Gregory D.} and Hirsch, {Alec J.} and Cody German and Smith, {Jessica L.} and Pinto, {Amelia K.}",

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doi = "10.1016/j.celrep.2022.110388",

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AU - Stone, E. Taylor

AU - Hassert, Mariah

AU - Geerling, Elizabeth

AU - Wagner, Colleen

AU - Brien, James D.

AU - Ebel, Gregory D.

AU - Hirsch, Alec J.

AU - German, Cody

AU - Smith, Jessica L.

AU - Pinto, Amelia K.

PY - 2022/2/15

Y1 - 2022/2/15

N2 - 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.

AB - 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.

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KW - immune protection

KW - murine model

KW - powassan virus

KW - tick-borne flavivirus

KW - tick-borne pathogens

KW - virus-like particle

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Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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