1. Epidemiology and Global Health
  2. Immunology and Inflammation

A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

  1. Yansheng Li
  2. Mingkai Xu  Is a corresponding author
  3. Yongqiang Li
  4. Wu Gu
  5. Gulinare Halimu
  6. Yuqi Li
  7. Zhichun Zhang
  8. Libao Zhou
  9. Hui Liao
  10. Songyuan Yao
  11. Huiwen Zhang
  12. Chenggang Zhang
  1. Chinese Academy of Sciences, China
  2. Chengda Biotechnology Co Ltd, China
https://doi.org/10.7554/eLife.71725
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Cite this article
  1. Yansheng Li
  2. Mingkai Xu
  3. Yongqiang Li
  4. Wu Gu
  5. Gulinare Halimu
  6. Yuqi Li
  7. Zhichun Zhang
  8. Libao Zhou
  9. Hui Liao
  10. Songyuan Yao
  11. Huiwen Zhang
  12. Chenggang Zhang
(2021)
A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
eLife 10:e71725.
https://doi.org/10.7554/eLife.71725
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  3. Download .RIS

Abstract

Influenza pandemics pose public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC which consist of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2, and Th17 subtypes. Mice vaccinated with NMHC produced high levels of immunoglobulins that cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtype) and group 2 (H3 subtype) influenza virus strains. Furthermore, purified anti-NMHC antibodies bound to multiple HAs with high affinities. NMHC vaccination effectively protected mice from infection and lung damage when exposed to two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T cell responses that cleared the virus from infected tissues and prevented virus spread. In conclusion, this study provides proof of concept that NMHC vaccination triggers B and T cell immune responses against multiple influenza virus infections. Therefore, NMHC might be a candidate universal broad-spectrum vaccine for the prevention and treatment of multiple influenza viruses.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Yansheng Li

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  2. Mingkai Xu

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    For correspondence
    mkxu@iae.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9889-6287

  3. Yongqiang Li

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  4. Wu Gu

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  5. Gulinare Halimu

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  6. Yuqi Li

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  7. Zhichun Zhang

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  8. Libao Zhou

    Chengda Biotechnology Co Ltd, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  9. Hui Liao

    Chengda Biotechnology Co Ltd, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  10. Songyuan Yao

    Chengda Biotechnology Co Ltd, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  11. Huiwen Zhang

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

  12. Chenggang Zhang

    Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang, China
    Competing interests
    The authors declare that no competing interests exist.

Funding

Strategic Priority Research Progrem of the Chinese Academy of Sciences Grant (XDA12020225)

  • Mingkai Xu

Liaoning Revitalization Talents Program (XLYC1807226)

  • Mingkai Xu

Science and Technolog Plan Projects of Shenyang City Grants (Z17-7-013)

  • Mingkai Xu

Shengyang High level Innovative Talents Program (RC190060)

  • Mingkai Xu

Science and Technology Agency Livelihood Program of Liaoning Province of China (2021JH2/10300075)

  • Mingkai Xu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health . All animal procedures were performed according to approved Institutional Animal Care and Use Committee (IACUC) guidelines of University of Chinese Academy of Sciences (permit-number IAE.No20191010A0120). All surgery was performed under tribromoethanol anesthesia, and every effort was made to minimize suffering.

Copyright

© 2021, Li et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yansheng Li
  2. Mingkai Xu
  3. Yongqiang Li
  4. Wu Gu
  5. Gulinare Halimu
  6. Yuqi Li
  7. Zhichun Zhang
  8. Libao Zhou
  9. Hui Liao
  10. Songyuan Yao
  11. Huiwen Zhang
  12. Chenggang Zhang
(2021)
A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection
eLife 10:e71725.
https://doi.org/10.7554/eLife.71725

Share this article

https://doi.org/10.7554/eLife.71725

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