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

Jeeva Subbiah; Judy Oh; Ki Hye Kim; Chong Hyun Shin; Bo Ryoung Park; Noopur Bhatnagar; Baik Lin Seong; Bao Zhong Wang; Sang Moo Kang

doi:10.1038/s41541-022-00498-6

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

Jeeva Subbiah, Judy Oh, Ki Hye Kim, Chong Hyun Shin, Bo Ryoung Park, Noopur Bhatnagar, Baik Lin Seong, Bao Zhong Wang, Sang Moo Kang

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

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.

Original language	English
Article number	68
Journal	npj Vaccines
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41541-022-00498-6
Publication status	Published - 2022 Dec

Bibliographical note

Funding Information:
NIH/NIAID grants AI093772 (S.-M.K.), AI154656 (S.-M.K.), and AI147042 (S.-M.K) partially supported this study. The following reagents were obtained from BEI Resources, NIAID, NIH: mouse adapted A/Fort Monmouth/1/1947 H1N1 (NR-28618), reassortant A/Nanchang/933/1995 H3N2 with A/PR8 backbone (NR-3692), A/Hong Kong/1/1968 H3N2 (NR-28634), and from IRR (International Reagent Resource): A/Hong Kong/1073/99 H9N2 influenza virus (FR-732).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

Immunology
Pharmacology
Infectious Diseases
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41541-022-00498-6

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title = "A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine",

abstract = "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.",

author = "Jeeva Subbiah and Judy Oh and Kim, {Ki Hye} and Shin, {Chong Hyun} and Park, {Bo Ryoung} and Noopur Bhatnagar and Seong, {Baik Lin} and Wang, {Bao Zhong} and Kang, {Sang Moo}",

note = "Funding Information: NIH/NIAID grants AI093772 (S.-M.K.), AI154656 (S.-M.K.), and AI147042 (S.-M.K) partially supported this study. The following reagents were obtained from BEI Resources, NIAID, NIH: mouse adapted A/Fort Monmouth/1/1947 H1N1 (NR-28618), reassortant A/Nanchang/933/1995 H3N2 with A/PR8 backbone (NR-3692), A/Hong Kong/1/1968 H3N2 (NR-28634), and from IRR (International Reagent Resource): A/Hong Kong/1073/99 H9N2 influenza virus (FR-732). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Bhatnagar, Noopur

AU - Seong, Baik Lin

AU - Wang, Bao Zhong

AU - Kang, Sang Moo

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

Abstract

Bibliographical note

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UN SDGs

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