A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Ryan J. Malonis; George I. Georgiev; Denise Haslwanter; Laura A. VanBlargan; Georgia Fallon; Olivia Vergnolle; Sean M. Cahill; Richard Harris; David Cowburn; Kartik Chandran; Michael S. Diamond; Jonathan R. Lai

doi:10.1371/journal.ppat.1010573

A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Ryan J. Malonis, George I. Georgiev, Denise Haslwanter, Laura A. VanBlargan, Georgia Fallon, Olivia Vergnolle, Sean M. Cahill, Richard Harris, David Cowburn, Kartik Chandran, Michael S. Diamond, Jonathan R. Lai

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

6 Scopus citations

Abstract

Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and CC⁰ loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.

Original language	English (US)
Article number	e1010573
Journal	PLoS pathogens
Volume	18
Issue number	6
DOIs	https://doi.org/10.1371/journal.ppat.1010573
State	Published - Jun 2022

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

UN SDGs

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

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10.1371/journal.ppat.1010573

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Malonis, R. J., Georgiev, G. I., Haslwanter, D., VanBlargan, L. A., Fallon, G., Vergnolle, O., Cahill, S. M., Harris, R., Cowburn, D., Chandran, K., Diamond, M. S., & Lai, J. R. (2022). A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice. PLoS pathogens, 18(6), Article e1010573. https://doi.org/10.1371/journal.ppat.1010573

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abstract = "Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and CC0 loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.",

author = "Malonis, {Ryan J.} and Georgiev, {George I.} and Denise Haslwanter and VanBlargan, {Laura A.} and Georgia Fallon and Olivia Vergnolle and Cahill, {Sean M.} and Richard Harris and David Cowburn and Kartik Chandran and Diamond, {Michael S.} and Lai, {Jonathan R.}",

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AU - Malonis, Ryan J.

AU - Georgiev, George I.

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AU - Fallon, Georgia

AU - Vergnolle, Olivia

AU - Cahill, Sean M.

AU - Harris, Richard

AU - Cowburn, David

AU - Chandran, Kartik

AU - Diamond, Michael S.

AU - Lai, Jonathan R.

N1 - Publisher Copyright: Copyright: © 2022 Malonis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/6

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N2 - Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and CC0 loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.

AB - Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and CC0 loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.

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A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

Abstract

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