A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants

  1. Jing Zhang
  2. Zi Bo Han
  3. Yu Liang
  4. Xue Feng Zhang
  5. Yu Qin Jin
  6. Li Fang Du
  7. Shuai Shao
  8. Hui Wang
  9. Jun Wei Hou
  10. Ke Xu
  11. Wenwen Lei
  12. Ze Hua Lei
  13. Zhao Ming Liu
  14. Jin Zhang
  15. Ya Nan Hou
  16. Ning Liu
  17. Fu Jie Shen
  18. Jin Juan Wu
  19. Xiang Zheng
  20. Xin Yu Li
  21. Xin Li
  22. Wei Jin Huang  Is a corresponding author
  23. Gui Zhen Wu  Is a corresponding author
  24. Ji Guo Su  Is a corresponding author
  25. Qi Ming Li  Is a corresponding author
  1. National Vaccine and Serum Institute, China
  2. Beijing Institute of Biological Products Company Limited, China
  3. Chinese Center For Disease Control and Prevention, China
  4. National Institutes for Food and Drug Control, China

Abstract

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Data availability

Figure 1 - Source Data 1, Figure 1 - Source Data 2, Figure 2 - Source Data 1, Figure 3 - Source Data 1 and Figure 4 - Source Data 1 contain the numerical data used to generate the figures. The gene sequence of the spike region of the Omicron BA.1.1 virus used in the live virus neutralization assay is provided in Appendix 1-figure 1, and the residue mutations in the Omicron BA.1.1 spike region compared to that of the prototype virus are provided in Appendix 1-figure 2.

Article and author information

Author details

  1. Jing Zhang

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Jing Zhang, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  2. Zi Bo Han

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Zi Bo Han, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  3. Yu Liang

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Yu Liang, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  4. Xue Feng Zhang

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Xue Feng Zhang, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  5. Yu Qin Jin

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Yu Qin Jin, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  6. Li Fang Du

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Li Fang Du, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  7. Shuai Shao

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Shuai Shao, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  8. Hui Wang

    Beijing Institute of Biological Products Company Limited, Beijing, China
    Competing interests
    Hui Wang, is an employee of Beijing Institute of Biological Products Company Limited..
  9. Jun Wei Hou

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Jun Wei Hou, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  10. Ke Xu

    National Institute for Viral Disease Control and Prevention, Chinese Center For Disease Control and Prevention, Beijing, China
    Competing interests
    No competing interests declared.
  11. Wenwen Lei

    National Institute for Viral Disease Control and Prevention, Chinese Center For Disease Control and Prevention, Beijing, China
    Competing interests
    No competing interests declared.
  12. Ze Hua Lei

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Ze Hua Lei, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  13. Zhao Ming Liu

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Zhao Ming Liu, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  14. Jin Zhang

    Beijing Institute of Biological Products Company Limited, Beijing, China
    Competing interests
    Jin Zhang, is an employee of Beijing Institute of Biological Products Company Limited..
  15. Ya Nan Hou

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Ya Nan Hou, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  16. Ning Liu

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Ning Liu, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  17. Fu Jie Shen

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    Fu Jie Shen, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  18. Jin Juan Wu

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    No competing interests declared.
  19. Xiang Zheng

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    No competing interests declared.
  20. Xin Yu Li

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    No competing interests declared.
  21. Xin Li

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    Competing interests
    No competing interests declared.
  22. Wei Jin Huang

    National Institutes for Food and Drug Control, Beijing, China
    For correspondence
    huangweijin@nifdc.org.cn
    Competing interests
    No competing interests declared.
  23. Gui Zhen Wu

    National Institute for Viral Disease Control and Prevention, Chinese Center For Disease Control and Prevention, Beijing, China
    For correspondence
    wugz@ivdc.chinacdc.cn
    Competing interests
    No competing interests declared.
  24. Ji Guo Su

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    For correspondence
    jiguosu@hotmail.com
    Competing interests
    Ji Guo Su, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
  25. Qi Ming Li

    The Sixth Laboratory, National Vaccine and Serum Institute, Beijing, China
    For correspondence
    liqiming189@163.com
    Competing interests
    Qi Ming Li, is listed as an inventor of the pending patent application for the mos-tri-RBD vaccine (Application number: 202210083654.X)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8284-7106

Funding

National Vaccine and Serum Institute (KTZC1900026C)

  • Jing Zhang

National Vaccine and Serum Institute (KTZC1900026C)

  • Qi Ming Li

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

Ethics

Animal experimentation: Animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of the National Vaccine and Serum Institute (NVSI) (No. NVSI-RCD-JSDW-ER-2021238, NVSI-RCD-JSDW-ER-2022015) and conducted under the regulations for the administration of affairs concerning experimental animals of China (2017).

Reviewing Editor

  1. Alex Sigal, University of KwaZulu-Natal, South Africa

Version history

  1. Received: March 14, 2022
  2. Preprint posted: March 29, 2022 (view preprint)
  3. Accepted: August 22, 2022
  4. Accepted Manuscript published: August 25, 2022 (version 1)
  5. Version of Record published: September 16, 2022 (version 2)

Copyright

© 2022, Zhang 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. Jing Zhang
  2. Zi Bo Han
  3. Yu Liang
  4. Xue Feng Zhang
  5. Yu Qin Jin
  6. Li Fang Du
  7. Shuai Shao
  8. Hui Wang
  9. Jun Wei Hou
  10. Ke Xu
  11. Wenwen Lei
  12. Ze Hua Lei
  13. Zhao Ming Liu
  14. Jin Zhang
  15. Ya Nan Hou
  16. Ning Liu
  17. Fu Jie Shen
  18. Jin Juan Wu
  19. Xiang Zheng
  20. Xin Yu Li
  21. Xin Li
  22. Wei Jin Huang
  23. Gui Zhen Wu
  24. Ji Guo Su
  25. Qi Ming Li
(2022)
A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants
eLife 11:e78633.
https://doi.org/10.7554/eLife.78633

Share this article

https://doi.org/10.7554/eLife.78633

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