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Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice
Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194115/ https://www.ncbi.nlm.nih.gov/pubmed/36302472 http://dx.doi.org/10.1016/j.virusres.2022.198991 |
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author | Chu, Julie TS Gu, Haogao Sun, Wanying Fan, Rebecca LY Nicholls, John M Valkenburg, Sophie A Poon, Leo LM |
author_facet | Chu, Julie TS Gu, Haogao Sun, Wanying Fan, Rebecca LY Nicholls, John M Valkenburg, Sophie A Poon, Leo LM |
author_sort | Chu, Julie TS |
collection | PubMed |
description | Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes. |
format | Online Article Text |
id | pubmed-10194115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-101941152023-05-19 Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice Chu, Julie TS Gu, Haogao Sun, Wanying Fan, Rebecca LY Nicholls, John M Valkenburg, Sophie A Poon, Leo LM Virus Res Article Rapid antigenic evolution of the influenza A virus surface antigen hemagglutinin undermines protection conferred by seasonal vaccines. Protective correlates targeted by universal vaccines such as cytotoxic T cells or HA stem directed broadly neutralizing antibodies have been shown to select for immune escape mutants during infection. We developed an in vivo serial passage mouse model for viral adaptation and used next generation sequencing to evaluate full genome viral evolution in the context of broadly protective immunity. Heterosubtypic immune pressure increased the incidence of genome-wide single nucleotide variants, though mutations found in early adapted populations were predominantly stochastic in nature. Prolonged adaptation under heterosubtypic immune selection resulted in the manifestation of highly virulent phenotypes that ablated vaccine mediated protection from mortality. High frequency mutations unique to escape phenotypes were identified within the polymerase encoding segments. These findings suggest that a suboptimial usage of population-wide universal influenza vaccine may drive formation of escape variants attributed to polygenic changes. Elsevier 2022-10-24 /pmc/articles/PMC10194115/ /pubmed/36302472 http://dx.doi.org/10.1016/j.virusres.2022.198991 Text en © 2023 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Chu, Julie TS Gu, Haogao Sun, Wanying Fan, Rebecca LY Nicholls, John M Valkenburg, Sophie A Poon, Leo LM Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title | Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title_full | Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title_fullStr | Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title_full_unstemmed | Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title_short | Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice |
title_sort | heterosubtypic immune pressure accelerates emergence of influenza a virus escape phenotypes in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194115/ https://www.ncbi.nlm.nih.gov/pubmed/36302472 http://dx.doi.org/10.1016/j.virusres.2022.198991 |
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