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An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets

There is a crucial need for an improved H3N2 influenza virus vaccine due to low vaccine efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. Here, we utilize a computational design strategy to produce epitope-optimized, broadly cross-reactive H3 hema...

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Autores principales: Bullard, Brianna L., DeBeauchamp, Jennifer, Pekarek, Matthew J., Petro-Turnquist, Erika, Vogel, Peter, Webby, Richard J., Weaver, Eric A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226166/
https://www.ncbi.nlm.nih.gov/pubmed/35739199
http://dx.doi.org/10.1038/s41541-022-00492-y
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author Bullard, Brianna L.
DeBeauchamp, Jennifer
Pekarek, Matthew J.
Petro-Turnquist, Erika
Vogel, Peter
Webby, Richard J.
Weaver, Eric A.
author_facet Bullard, Brianna L.
DeBeauchamp, Jennifer
Pekarek, Matthew J.
Petro-Turnquist, Erika
Vogel, Peter
Webby, Richard J.
Weaver, Eric A.
author_sort Bullard, Brianna L.
collection PubMed
description There is a crucial need for an improved H3N2 influenza virus vaccine due to low vaccine efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. Here, we utilize a computational design strategy to produce epitope-optimized, broadly cross-reactive H3 hemagglutinins in order to create a universal H3N2 influenza vaccine. The Epigraph immunogens are designed to maximize the viral population frequency of epitopes incorporated into the immunogen. We compared our Epigraph H3 vaccine to the traditional egg-based inactivated influenza vaccine from 2018–19, FluZone. Epigraph vaccination-induced stronger cross-reactive antibody responses than FluZone against 18 H3N2 viruses isolated from 1968 to 2019 in both mice and ferrets, with protective hemagglutination inhibition titers against 93–100% of the contemporary H3N2 strains compared to only 27% protection measured from FluZone. In addition, Epigraph vaccination-induced strong cross-reactive T-cell immunity which significantly contributes to protection against lethal influenza virus infection. Finally, Epigraph vaccination protected ferrets from influenza disease after challenge with two H3N2 viruses. The superior cross-reactive immunity induced by these Epigraph immunogens supports their development as a universal H3N2 influenza vaccine.
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spelling pubmed-92261662022-06-25 An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets Bullard, Brianna L. DeBeauchamp, Jennifer Pekarek, Matthew J. Petro-Turnquist, Erika Vogel, Peter Webby, Richard J. Weaver, Eric A. NPJ Vaccines Article There is a crucial need for an improved H3N2 influenza virus vaccine due to low vaccine efficacy rates and increased morbidity and mortality associated with H3N2-dominated influenza seasons. Here, we utilize a computational design strategy to produce epitope-optimized, broadly cross-reactive H3 hemagglutinins in order to create a universal H3N2 influenza vaccine. The Epigraph immunogens are designed to maximize the viral population frequency of epitopes incorporated into the immunogen. We compared our Epigraph H3 vaccine to the traditional egg-based inactivated influenza vaccine from 2018–19, FluZone. Epigraph vaccination-induced stronger cross-reactive antibody responses than FluZone against 18 H3N2 viruses isolated from 1968 to 2019 in both mice and ferrets, with protective hemagglutination inhibition titers against 93–100% of the contemporary H3N2 strains compared to only 27% protection measured from FluZone. In addition, Epigraph vaccination-induced strong cross-reactive T-cell immunity which significantly contributes to protection against lethal influenza virus infection. Finally, Epigraph vaccination protected ferrets from influenza disease after challenge with two H3N2 viruses. The superior cross-reactive immunity induced by these Epigraph immunogens supports their development as a universal H3N2 influenza vaccine. Nature Publishing Group UK 2022-06-23 /pmc/articles/PMC9226166/ /pubmed/35739199 http://dx.doi.org/10.1038/s41541-022-00492-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bullard, Brianna L.
DeBeauchamp, Jennifer
Pekarek, Matthew J.
Petro-Turnquist, Erika
Vogel, Peter
Webby, Richard J.
Weaver, Eric A.
An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title_full An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title_fullStr An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title_full_unstemmed An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title_short An epitope-optimized human H3N2 influenza vaccine induces broadly protective immunity in mice and ferrets
title_sort epitope-optimized human h3n2 influenza vaccine induces broadly protective immunity in mice and ferrets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226166/
https://www.ncbi.nlm.nih.gov/pubmed/35739199
http://dx.doi.org/10.1038/s41541-022-00492-y
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