Protective efficacy of anti-neuraminidase monoclonal antibodies against H7N9 influenza virus infection

Fei-Fei Xiong; Xue-Ying Liu; Fei-Xia Gao; Jian Luo; Peng Duan; Wen-Song Tan; Ze Chen

doi:10.1080/22221751.2019.1708214

Protective efficacy of anti-neuraminidase monoclonal antibodies against H7N9 influenza virus infection

Emerg Microbes Infect. 2020 Jan 2;9(1):78-87. doi: 10.1080/22221751.2019.1708214. eCollection 2020.

Authors

Fei-Fei Xiong¹, Xue-Ying Liu¹, Fei-Xia Gao^{1

2}, Jian Luo¹, Peng Duan¹, Wen-Song Tan², Ze Chen¹

Affiliations

¹ Shanghai Institute of Biological Products, Shanghai, People's Republic of China.
² East China University of Science and Technology, Shanghai, People's Republic of China.

Abstract

The H7N9 influenza virus has been circulating in China for more than six years. The neuraminidase (NA) has gained great concern for the development of antiviral drugs, therapeutic antibodies, and new vaccines. In this study, we screened seven mouse monoclonal antibodies (mAbs) and compared their protective effects against H7N9 influenza virus. The epitope mapping from escape mutants showed that all the seven mAbs could bind to the head region of the N9 NA close to the enzyme activity sites, and four key sites of N9 NA were reported for the first time. The mAbs D3 and 7H2 could simultaneously inhibit the cleavage of the sialic acid of fetuin protein with large molecular weight and NA-XTD with small molecule weight in the NA inhibition experiment, prevent the formation of virus plaque at a low concentration, and effectively protect the mice from the challenge of the lethal dose of H7N9 virus.

Keywords: H7N9 influenza virus; NA epitope; monoclonal antibodies; neuraminidase; protection.

MeSH terms

Animals
Antibodies, Monoclonal / chemistry*
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / therapeutic use
Antigens, Viral
Catalytic Domain
Cell Line
Dogs
Epitope Mapping
Humans
Influenza A Virus, H7N9 Subtype / immunology*
Influenza, Human / drug therapy
Influenza, Human / prevention & control
Mice
Mice, Inbred BALB C
Neuraminidase / antagonists & inhibitors*
Neuraminidase / chemistry*
Orthomyxoviridae Infections / drug therapy
Orthomyxoviridae Infections / prevention & control*

Substances

Antibodies, Monoclonal
Antigens, Viral
Neuraminidase

Grants and funding

This work was supported by grants from the National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology, China under Grant [2015ZX09101044] and Science and Technology Commission of Shanghai Municipality, China under Grants [15431906500 and 17431901300].