A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine

We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expres...

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Autores principales: Subbiah, Jeeva, Oh, Judy, Kim, Ki-Hye, Shin, Chong-Hyun, Park, Bo Ryoung, Bhatnagar, Noopur, Seong, Baik-Lin, Wang, Bao-Zhong, Kang, Sang-Moo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243060/
https://www.ncbi.nlm.nih.gov/pubmed/35768475
http://dx.doi.org/10.1038/s41541-022-00498-6
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author Subbiah, Jeeva
Oh, Judy
Kim, Ki-Hye
Shin, Chong-Hyun
Park, Bo Ryoung
Bhatnagar, Noopur
Seong, Baik-Lin
Wang, Bao-Zhong
Kang, Sang-Moo
author_facet Subbiah, Jeeva
Oh, Judy
Kim, Ki-Hye
Shin, Chong-Hyun
Park, Bo Ryoung
Bhatnagar, Noopur
Seong, Baik-Lin
Wang, Bao-Zhong
Kang, Sang-Moo
author_sort Subbiah, Jeeva
collection PubMed
description We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expressed and purified from Escherichia coli was thermostable, displaying native-like antigenic epitopes recognized by antisera of different HA subtype proteins and influenza A virus infections. Adjuvanted M2e-H3 stalk vaccination induced M2e and stalk-specific IgG antibodies recognizing viral antigens on virus particles and on the infected cell surface, CD4(+) and CD8(+) T-cell responses, and antibody-dependent cytotoxic cell surrogate activity in mice. M2e-H3 stalk was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, H7N9) at similar levels in adult and aged mice. These results provide evidence that M2e-H3 stalk chimeric proteins can be developed as a universal influenza A virus vaccine candidate for young and aged populations.
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spelling pubmed-92430602022-07-01 A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine Subbiah, Jeeva Oh, Judy Kim, Ki-Hye Shin, Chong-Hyun Park, Bo Ryoung Bhatnagar, Noopur Seong, Baik-Lin Wang, Bao-Zhong Kang, Sang-Moo NPJ Vaccines Article We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expressed and purified from Escherichia coli was thermostable, displaying native-like antigenic epitopes recognized by antisera of different HA subtype proteins and influenza A virus infections. Adjuvanted M2e-H3 stalk vaccination induced M2e and stalk-specific IgG antibodies recognizing viral antigens on virus particles and on the infected cell surface, CD4(+) and CD8(+) T-cell responses, and antibody-dependent cytotoxic cell surrogate activity in mice. M2e-H3 stalk was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, H7N9) at similar levels in adult and aged mice. These results provide evidence that M2e-H3 stalk chimeric proteins can be developed as a universal influenza A virus vaccine candidate for young and aged populations. Nature Publishing Group UK 2022-06-29 /pmc/articles/PMC9243060/ /pubmed/35768475 http://dx.doi.org/10.1038/s41541-022-00498-6 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
Subbiah, Jeeva
Oh, Judy
Kim, Ki-Hye
Shin, Chong-Hyun
Park, Bo Ryoung
Bhatnagar, Noopur
Seong, Baik-Lin
Wang, Bao-Zhong
Kang, Sang-Moo
A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title_full A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title_fullStr A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title_full_unstemmed A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title_short A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
title_sort chimeric thermostable m2e and h3 stalk-based universal influenza a virus vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243060/
https://www.ncbi.nlm.nih.gov/pubmed/35768475
http://dx.doi.org/10.1038/s41541-022-00498-6
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