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

doi:10.1038/s41467-024-47213-8

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

Nat Commun. 2024 Apr 6;15(1):2987. doi: 10.1038/s41467-024-47213-8.

Authors

Li Chen^#^{1

2}, Mengmeng Sun^#³, Huajun Zhang^#¹, Xinghai Zhang^#¹, Yanfeng Yao^#¹, Ming Li³, Kangyin Li^{1

2}, Pengfei Fan⁴, Haiwei Zhang¹, Ye Qin^{1

2}, Zhe Zhang¹, Entao Li^{3

5

6}, Zhen Chen¹, Wuxiang Guan¹, Shanshan Li³, Changming Yu⁷, Kaiming Zhang^{8

9

10

11}, Rui Gong^{12

13

14}, Sandra Chiu^{15

16

17}

Affiliations

¹ CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, Hubei, China.
² University of Chinese Academy of Sciences, Beijing, China.
³ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
⁴ Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China.
⁵ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
⁶ Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, China.
⁷ Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing, China. yuchangming@126.com.
⁸ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. kmzhang@ustc.edu.cn.
⁹ Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, China. kmzhang@ustc.edu.cn.
¹⁰ Center for Advanced Interdisciplinary Science and Biomedicine of IHM, MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. kmzhang@ustc.edu.cn.
¹¹ Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. kmzhang@ustc.edu.cn.
¹² 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.
¹³ University of Chinese Academy of Sciences, Beijing, China. gongr@wh.iov.cn.
¹⁴ Hubei Jiangxia Laboratory, Wuhan, Hubei, China. gongr@wh.iov.cn.
¹⁵ Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. qiux@ustc.edu.cn.
¹⁶ Department of Laboratory Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China. qiux@ustc.edu.cn.
¹⁷ Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, China. qiux@ustc.edu.cn.

^# Contributed equally.

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.

MeSH terms

Antibodies, Neutralizing / metabolism
Antibodies, Viral
Henipavirus Infections*
Humans
Nipah Virus* / metabolism

Substances

Antibodies, Neutralizing
Antibodies, Viral