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Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages

A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from...

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Autores principales: Gravel, Caroline, Muralidharan, Abenaya, Duran, Amparo, Zetner, Adrian, Pfeifle, Annabelle, Zhang, Wanyue, Hashem, Anwar, Tamming, Levi, Farnsworth, Aaron, Loemba, Hugues, Chen, Wangxue, Krammer, Florian, Safronetz, David, Cao, Jingxin, Wang, Lisheng, Sauve, Simon, Rosu-Myles, Michael, Van Domselaar, Gary, Li, Xuguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586812/
https://www.ncbi.nlm.nih.gov/pubmed/34805790
http://dx.doi.org/10.1016/j.isci.2021.103328
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author Gravel, Caroline
Muralidharan, Abenaya
Duran, Amparo
Zetner, Adrian
Pfeifle, Annabelle
Zhang, Wanyue
Hashem, Anwar
Tamming, Levi
Farnsworth, Aaron
Loemba, Hugues
Chen, Wangxue
Krammer, Florian
Safronetz, David
Cao, Jingxin
Wang, Lisheng
Sauve, Simon
Rosu-Myles, Michael
Van Domselaar, Gary
Li, Xuguang
author_facet Gravel, Caroline
Muralidharan, Abenaya
Duran, Amparo
Zetner, Adrian
Pfeifle, Annabelle
Zhang, Wanyue
Hashem, Anwar
Tamming, Levi
Farnsworth, Aaron
Loemba, Hugues
Chen, Wangxue
Krammer, Florian
Safronetz, David
Cao, Jingxin
Wang, Lisheng
Sauve, Simon
Rosu-Myles, Michael
Van Domselaar, Gary
Li, Xuguang
author_sort Gravel, Caroline
collection PubMed
description A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.
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spelling pubmed-85868122021-11-19 Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages Gravel, Caroline Muralidharan, Abenaya Duran, Amparo Zetner, Adrian Pfeifle, Annabelle Zhang, Wanyue Hashem, Anwar Tamming, Levi Farnsworth, Aaron Loemba, Hugues Chen, Wangxue Krammer, Florian Safronetz, David Cao, Jingxin Wang, Lisheng Sauve, Simon Rosu-Myles, Michael Van Domselaar, Gary Li, Xuguang iScience Article A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection. Elsevier 2021-10-21 /pmc/articles/PMC8586812/ /pubmed/34805790 http://dx.doi.org/10.1016/j.isci.2021.103328 Text en Crown Copyright © 2021. 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
Gravel, Caroline
Muralidharan, Abenaya
Duran, Amparo
Zetner, Adrian
Pfeifle, Annabelle
Zhang, Wanyue
Hashem, Anwar
Tamming, Levi
Farnsworth, Aaron
Loemba, Hugues
Chen, Wangxue
Krammer, Florian
Safronetz, David
Cao, Jingxin
Wang, Lisheng
Sauve, Simon
Rosu-Myles, Michael
Van Domselaar, Gary
Li, Xuguang
Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title_full Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title_fullStr Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title_full_unstemmed Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title_short Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages
title_sort synthetic vaccine affords full protection to mice against lethal challenge of influenza b virus of both genetic lineages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586812/
https://www.ncbi.nlm.nih.gov/pubmed/34805790
http://dx.doi.org/10.1016/j.isci.2021.103328
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