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Nature communications
Apr 06, 2024;15 (1): 2987.

Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains.

Li Chen, Mengmeng Sun, Huajun Zhang, Xinghai Zhang, Yanfeng Yao, Ming Li, Kangyin Li, Pengfei Fan, Haiwei Zhang, Ye Qin, Zhe Zhang, Entao Li, Zhen Chen, Wuxiang Guan, Shanshan Li, Changming Yu, Kaiming Zhang, Rui Gong, Sandra Chiu
Author Information
  1. Li Chen: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. ORCID
  2. Mengmeng Sun: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  3. Huajun Zhang: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. ORCID
  4. Xinghai Zhang: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  5. Yanfeng Yao: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. ORCID
  6. Ming Li: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  7. Kangyin Li: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  8. Pengfei Fan: Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China. ORCID
  9. Haiwei Zhang: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  10. Ye Qin: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  11. Zhe Zhang: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  12. Entao Li: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  13. Zhen Chen: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  14. Wuxiang Guan: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
  15. Shanshan Li: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. ORCID
  16. Changming Yu: Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China. yuchangming@126.com. ORCID
  17. Kaiming Zhang: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. kmzhang@ustc.edu.cn. ORCID
  18. Rui Gong: CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China. gongr@wh.iov.cn. ORCID
  19. Sandra Chiu: Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. qiux@ustc.edu.cn. ORCID
PMID: 38582870 DOI: 10.1038/s41467-024-47213-8

Abstract

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.

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MeSH Term

Humans
Antibodies, Neutralizing
Nipah Virus
Antibodies, Viral
Henipavirus Infections

Chemicals

Antibodies, Neutralizing
Antibodies, Viral
Journal Article
Article has an altmetric score of 7

Word Cloud

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