puc-header

A Potent Germline-Like Human Monoclonal Antibody Targeting a Novel pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin

51 Pages Posted: 6 Apr 2018 Sneak Peek Status: Published

See all articles by Fei Yu

Fei Yu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

He Song

Government of the United States of America - Macromolecular Crystallography Laboratory

Yanling Wu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

So Young Chang

Institut Pasteur Korea - Respiratory Viruses Research Laboratory

Lili Wang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

Shuai Xia

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS); Fudan University - Shanghai Public Health Clinical Center

Binbin Hong

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

Wei Li

Government of the United States of America - Protein Interactions Section

Chunyu Wang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

Surender Khurana

Government of the United States of America - Division of Viral Products

Yang Feng

Government of the United States of America - Protein Interactions Section

Yanping Wang

Government of the United States of America - Protein Interactions Section

Zhiwu Sun

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

Biao He

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

Jody Manischewitz

Government of the United States of America - Division of Viral Products

Lisa R. King

Government of the United States of America - Division of Viral Products

Ji-Young Min

Institut Pasteur Korea - Respiratory Viruses Research Laboratory

Hana Golding

Government of the United States of America - Division of Viral Products

Xinhua Ji

Government of the United States of America - Macromolecular Crystallography Laboratory

Lu Lu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS); Fudan University - Shanghai Public Health Clinical Center

Shibo Jiang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS); Fudan University - Shanghai Public Health Clinical Center

Dimiter S. Dimitrov

Government of the United States of America - Protein Interactions Section

Tianlei Ying

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

More...

Abstract

The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a novel human monoclonal antibody, m826, which bound to H7 hemagglutinin (HA) with subnanomolar affinity at pH 5.0 and 10-fold lower affinity at neutral pH. The high-resolution (1.9 Å) crystal structure of m826 complexed with H7N9 HA indicated that m826 binds to a novel unique epitope which could explain its pH sensitivity. Furthermore, m826 fully protected mice against lethal challenge of H7N9 virus, indicating that m826 is highly effective in vivo likely due to its ability to induce potent ADCC. Interestingly, immunogenetic analysis indicated that m826 is a germline antibody and m826-like sequences can be identified in H7N9-infected patients, healthy adults and newborn babies. The unique m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a new tool for exploring mechanisms of virus infection inhibition by antibodies.

Suggested Citation

Yu, Fei and Song, He and Wu, Yanling and Chang, So Young and Wang, Lili and Xia, Shuai and Hong, Binbin and Li, Wei and Wang, Chunyu and Khurana, Surender and Feng, Yang and Wang, Yanping and Sun, Zhiwu and He, Biao and Manischewitz, Jody and King, Lisa R. and Min, Ji-Young and Golding, Hana and Ji, Xinhua and Lu, Lu and Jiang, Shibo and Dimitrov, Dimiter S. and Ying, Tianlei, A Potent Germline-Like Human Monoclonal Antibody Targeting a Novel pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin (2018). Available at SSRN: https://ssrn.com/abstract=3155911 or http://dx.doi.org/10.2139/ssrn.3155911
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Fei Yu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

He Song

Government of the United States of America - Macromolecular Crystallography Laboratory

National Cancer Institute
Building 536, Room 4
Frederick, MD 21702-1201
United States

Yanling Wu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

So Young Chang

Institut Pasteur Korea - Respiratory Viruses Research Laboratory

Gyeonggi-do, 463400
Korea, Republic of (South Korea)

Lili Wang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Shuai Xia

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Binbin Hong

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Wei Li

Government of the United States of America - Protein Interactions Section

Frederick, MD 21701-1201
United States

Chunyu Wang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Surender Khurana

Government of the United States of America - Division of Viral Products

Silver Spring, MD 20993
United States

Yang Feng

Government of the United States of America - Protein Interactions Section

Frederick, MD 21701-1201
United States

Yanping Wang

Government of the United States of America - Protein Interactions Section

Frederick, MD 21701-1201
United States

Zhiwu Sun

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Biao He

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Jody Manischewitz

Government of the United States of America - Division of Viral Products

Silver Spring, MD 20993
United States

Lisa R. King

Government of the United States of America - Division of Viral Products

Silver Spring, MD 20993
United States

Ji-Young Min

Institut Pasteur Korea - Respiratory Viruses Research Laboratory

Gyeonggi-do, 463400
Korea, Republic of (South Korea)

Hana Golding

Government of the United States of America - Division of Viral Products

Silver Spring, MD 20993
United States

Xinhua Ji

Government of the United States of America - Macromolecular Crystallography Laboratory

National Cancer Institute
Building 536, Room 4
Frederick, MD 21702-1201
United States

Lu Lu

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Shibo Jiang

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS)

138 Dong’an Rd
Shanghai, 200032
China

Fudan University - Shanghai Public Health Clinical Center

Shanghai
China

Dimiter S. Dimitrov

Government of the United States of America - Protein Interactions Section

Frederick, MD 21701-1201
United States

Tianlei Ying (Contact Author)

Fudan University - Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS) ( email )

138 Dong’an Rd
Shanghai, 200032
China

Click here to go to Cell.com

Paper statistics

Abstract Views
341
Downloads
5