Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin

Abstract Hemagglutinin (HA)-based current vaccines provide suboptimum cross protection. Influenza A virus contains an ion channel protein M2 conserved extracellular domain (M2e), a target for developing universal vaccines. Here we generated reassortant influenza virus rgH3N2 4xM2e virus (HA and NA f...

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Autores principales:	Bo Ryoung Park, Ki-Hye Kim, Tatiana Kotomina, Min-Chul Kim, Young-Man Kwon, Subbiah Jeeva, Yu-Jin Jung, Noopur Bhatnagar, Irina Isakova-Sivak, Daria Mezhenskaya, Larisa Rudenko, Bao-Zhong Wang, Sang-Moo Kang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de27ac60c5a6402b8c6c3bb5e7a6fea3
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spelling	oai:doaj.org-article:de27ac60c5a6402b8c6c3bb5e7a6fea32021-12-02T10:54:31ZBroad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin10.1038/s41598-021-83704-02045-2322https://doaj.org/article/de27ac60c5a6402b8c6c3bb5e7a6fea32021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83704-0https://doaj.org/toc/2045-2322Abstract Hemagglutinin (HA)-based current vaccines provide suboptimum cross protection. Influenza A virus contains an ion channel protein M2 conserved extracellular domain (M2e), a target for developing universal vaccines. Here we generated reassortant influenza virus rgH3N2 4xM2e virus (HA and NA from A/Switzerland/9715293/2013/(H3N2)) expressing chimeric 4xM2e-HA fusion proteins with 4xM2e epitopes inserted into the H3 HA N-terminus. Recombinant rgH3N2 4xM2e virus was found to retain equivalent growth kinetics as rgH3N2 in egg substrates. Intranasal single inoculation of mice with live rgH3N2 4xM2e virus was effective in priming the induction of M2e specific IgG antibody responses in mucosal and systemic sites as well as T cell responses. The rgH3N2 4xM2e primed mice were protected against a broad range of different influenza A virus subtypes including H1N1, H3N2, H5N1, H7N9, and H9N2. The findings support a new approach to improve the efficacy of current vaccine platforms by recombinant influenza virus inducing immunity to HA and cross protective M2e antigens.Bo Ryoung ParkKi-Hye KimTatiana KotominaMin-Chul KimYoung-Man KwonSubbiah JeevaYu-Jin JungNoopur BhatnagarIrina Isakova-SivakDaria MezhenskayaLarisa RudenkoBao-Zhong WangSang-Moo KangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bo Ryoung Park Ki-Hye Kim Tatiana Kotomina Min-Chul Kim Young-Man Kwon Subbiah Jeeva Yu-Jin Jung Noopur Bhatnagar Irina Isakova-Sivak Daria Mezhenskaya Larisa Rudenko Bao-Zhong Wang Sang-Moo Kang Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
description	Abstract Hemagglutinin (HA)-based current vaccines provide suboptimum cross protection. Influenza A virus contains an ion channel protein M2 conserved extracellular domain (M2e), a target for developing universal vaccines. Here we generated reassortant influenza virus rgH3N2 4xM2e virus (HA and NA from A/Switzerland/9715293/2013/(H3N2)) expressing chimeric 4xM2e-HA fusion proteins with 4xM2e epitopes inserted into the H3 HA N-terminus. Recombinant rgH3N2 4xM2e virus was found to retain equivalent growth kinetics as rgH3N2 in egg substrates. Intranasal single inoculation of mice with live rgH3N2 4xM2e virus was effective in priming the induction of M2e specific IgG antibody responses in mucosal and systemic sites as well as T cell responses. The rgH3N2 4xM2e primed mice were protected against a broad range of different influenza A virus subtypes including H1N1, H3N2, H5N1, H7N9, and H9N2. The findings support a new approach to improve the efficacy of current vaccine platforms by recombinant influenza virus inducing immunity to HA and cross protective M2e antigens.
format	article
author	Bo Ryoung Park Ki-Hye Kim Tatiana Kotomina Min-Chul Kim Young-Man Kwon Subbiah Jeeva Yu-Jin Jung Noopur Bhatnagar Irina Isakova-Sivak Daria Mezhenskaya Larisa Rudenko Bao-Zhong Wang Sang-Moo Kang
author_facet	Bo Ryoung Park Ki-Hye Kim Tatiana Kotomina Min-Chul Kim Young-Man Kwon Subbiah Jeeva Yu-Jin Jung Noopur Bhatnagar Irina Isakova-Sivak Daria Mezhenskaya Larisa Rudenko Bao-Zhong Wang Sang-Moo Kang
author_sort	Bo Ryoung Park
title	Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
title_short	Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
title_full	Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
title_fullStr	Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
title_full_unstemmed	Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin
title_sort	broad cross protection by recombinant live attenuated influenza h3n2 seasonal virus expressing conserved m2 extracellular domain in a chimeric hemagglutinin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de27ac60c5a6402b8c6c3bb5e7a6fea3
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Broad cross protection by recombinant live attenuated influenza H3N2 seasonal virus expressing conserved M2 extracellular domain in a chimeric hemagglutinin

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