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Article | Open Access

A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites Ⅳ and Ⅴ of the viral fusion glycoprotein

Lianpan Dai1,#, Jian Song1,#, Lili Xu2,#, Zhao Gao3,#, Senyu Xu4,#, Yan Chai1, Liang Wang1, Mi Yang1, Tong Ma1, Qihui Wang1, Sushan Cao3, Junming Yie3, Gang Zou3, Zhengde Xie2( ), Jim Zhen Wu3( ), George Fu Gao1,4( )
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Research Unit of Critical Infection in Children, Chinese Academy of Medical Sciences, 2019RU016, Laboratory of Infection and Virology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Shanghai Ark Biopharmaceutical Co., Ltd., Shanghai, China
Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China

# These authors contributed equally to this work

Show Author Information

Highlights

● Isolation of human neutralizing antibodies against RSV from the convalescent children.

● One potent monoclonal antibody RV11 potently neutralizes both RSV A and B subtypes.

● RV11 binds to a conserved epitope across site Ⅳ/Ⅴ of the fusion glycoprotein in its prefusion state.

● RV11 is synergistic with a small molecular inhibitor ziresovir and a site Ø neutralizing mAb.

Graphical Abstract

Abstract

Respiratory syncytial virus (RSV) is one of the leading pathogens that cause lower respiratory tract infections in infants and the elderly. Passive immunoprophylaxis with monoclonal antibody (mAb) has been approved to prevent morbidity and mortality from RSV infection in infants. Here we report the isolation of two neutralizing mAbs against RSV from convalescent children by prefusion form of fusion (F) glycoprotein as bait. One mAb RV11 exhibited good potency in neutralization of RSV strains from both A and B subtypes in cell-based assay, and protected mice from RSV infection in vivo. An RV11 escape mutant was identified, which contains an S443P mutation in F protein. Crystal structure showed the RV11 bound to a conserved prefusion epitope across the antigenic sites Ⅳ and Ⅴ of the F glycoprotein. RV11 showed a strong synergistic effect when combined with two RSV antivirals, an F-targeting small molecular inhibitor ziresovir and a site Ø neutralizing mAb D25 (the parental mAb for nirsevimab). The study extended our knowledge to the neutralizing and protective epitopes of RSV, and the mAb RV11 deserves further development for clinical translation.

Keywords

Respiratory syncytial virus (RSV) antibodyRSV monoclonal antibodyRSV fusion glycoproteinRSV epitopepalivizumabRSV prophylaxis

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hLife
Volume 1 Issue 1,
November 2023
Pages 12-25
DOI: 10.1016/j.hlife.2023.09.003
Cite this article:
Dai L, Song J, Xu L, et al. A protective human antibody against respiratory syncytial virus by targeting a prefusion epitope across sites Ⅳ and Ⅴ of the viral fusion glycoprotein. hLife, 2023, 1(1): 12-25. https://doi.org/10.1016/j.hlife.2023.09.003

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Received: 12 August 2023
Revised: 26 September 2023
Accepted: 27 September 2023
Published: 28 September 2023
© 2023 The Author(s).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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