Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses

Tingting Li; Junyu Chen; Qingbing Zheng; Wenhui Xue; Limin Zhang; Rui Rong; Sibo Zhang; Qian Wang; Minqing Hong; Yuyun Zhang; Lingyan Cui; Maozhou He; Zhen Lu; Zhenyong Zhang; Xin Chi; Jinjin Li; Yang Huang; Hong Wang; Jixian Tang; Dong Ying; Lizhi Zhou; Yingbin Wang; Hai Yu; Jun Zhang; Ying Gu; Yixin Chen; Shaowei Li; Ningshao Xia

doi:10.1038/s41467-022-32926-5

Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses

Nat Commun. 2022 Sep 2;13(1):5182. doi: 10.1038/s41467-022-32926-5.

Authors

Tingting Li^#^{1

2}, Junyu Chen^#^{1

2}, Qingbing Zheng^#^{1

2}, Wenhui Xue^#^{1

2}, Limin Zhang^#^{1

2}, Rui Rong^{1

2}, Sibo Zhang^{1

2}, Qian Wang^{1

2}, Minqing Hong^{1

2}, Yuyun Zhang^{1

2}, Lingyan Cui^{1

2}, Maozhou He^{1

2}, Zhen Lu^{1

2}, Zhenyong Zhang^{1

2}, Xin Chi^{1

2}, Jinjin Li^{1

2}, Yang Huang^{1

2}, Hong Wang^{1

2}, Jixian Tang^{1

2}, Dong Ying^{1

2}, Lizhi Zhou^{1

2}, Yingbin Wang^{1

2}, Hai Yu^{1

2}, Jun Zhang^{1

2}, Ying Gu^{3

4}, Yixin Chen^{5

6}, Shaowei Li^{7

8}, Ningshao Xia^{9

10

11}

Affiliations

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China.
² National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China.
³ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China. guying@xmu.edu.cn.
⁴ National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China. guying@xmu.edu.cn.
⁵ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China. yxchen2008@xmu.edu.cn.
⁶ National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China. yxchen2008@xmu.edu.cn.
⁷ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China. shaowei@xmu.edu.cn.
⁸ National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China. shaowei@xmu.edu.cn.
⁹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, School of Public Health, Xiamen University, 361102, Xiamen, Fujian, China. nsxia@xmu.edu.cn.
¹⁰ National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, 361102, Xiamen, Fujian, China. nsxia@xmu.edu.cn.
¹¹ Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences, 361102, Xiamen, Fujian, China. nsxia@xmu.edu.cn.

^# Contributed equally.

Abstract

Influenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Binding Sites
Broadly Neutralizing Antibodies
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Influenza A Virus, H1N1 Subtype*
Influenza A Virus, H5N1 Subtype*
Influenza Vaccines*
Influenza, Human*
Orthomyxoviridae Infections*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Broadly Neutralizing Antibodies
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines