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Broadly Neutralizing Antibodies Against Conserved Epitopes of the Hemagglutinin Head are Robustly Recalled by a Novel H1N1 Virus

60 Pages Posted: 24 Nov 2020 Publication Status: Review Complete

See all articles by Jenna J. Guthmiller

Jenna J. Guthmiller

University of Chicago - Section of Rheumatology

Julianna Han

The Scripps Research Institute - Department of Integrative Structural and Computational Biology

Lei Li

University of Chicago - Section of Rheumatology

Alec W. Freyn

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Sean T.H. Liu

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Olivia Stovicek

University of Chicago - Section of Rheumatology

Christopher Stamper

University of Chicago - Committee on Immunology

Haley L. Dugan

University of Chicago - Committee on Immunology

Micah E. Tepora

University of Chicago - Section of Rheumatology

Dalia J. Bitar

University of Chicago - Section of Rheumatology

Natalie J. Hamel

University of Chicago - Section of Rheumatology

Siriruk Changrob

University of Chicago - Section of Rheumatology

Nai-Ying Zheng

University of Chicago - Section of Rheumatology

Min Huang

University of Chicago - Section of Rheumatology

Henry A. Utset

University of Chicago - Section of Rheumatology

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Raffael Nachbagauer

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Peter Palese

Icahn School of Medicine at Mount Sinai - Department of Microbiology

Andrew B. Ward

The Scripps Research Institute - Department of Integrative Structural and Computational Biology; The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; The Scripps Research Institute - IAVI Neutralizing Antibody Center

Patrick C. Wilson

University of Chicago - Section of Rheumatology

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Abstract

Broadly neutralizing antibodies are critical for protection against drifted and novel influenza viruses. Here, we reveal humans have pre-existing immunity against two broadly neutralizing epitopes of the HA head: the lateral patch and receptor-binding site (RBS). Monoclonal antibodies generated against these epitopes are broadly neutralizing against 40+ years of H1N1 evolution and provide potent protection in vivo. First exposure to the novel 2009 pandemic H1N1 virus recalls memory B cells that target the conserved RBS and lateral patch epitopes. We identified unique repertoire, structural, and binding features of lateral patch and RBS binding antibodies including a lateral patch binding motif shared across subjects. Together, our data indicate that the conserved RBS and lateral patch epitopes are readily targeted by the human memory B cell pool and that universal vaccine strategies should aim to drive antibodies against both conserved head and stalk domain epitopes.

Keywords: H1N1; hemagglutinin head; lateral patch; receptor-binding site; broadly neutralizing antibodies

Suggested Citation

Guthmiller, Jenna J. and Han, Julianna and Li, Lei and Freyn, Alec W. and Liu, Sean T.H. and Stovicek, Olivia and Stamper, Christopher and Dugan, Haley L. and Tepora, Micah E. and Bitar, Dalia J. and Hamel, Natalie J. and Changrob, Siriruk and Zheng, Nai-Ying and Huang, Min and Utset, Henry A. and Krammer, Florian and Nachbagauer, Raffael and Palese, Peter and Ward, Andrew B. and Wilson, Patrick C., Broadly Neutralizing Antibodies Against Conserved Epitopes of the Hemagglutinin Head are Robustly Recalled by a Novel H1N1 Virus. Available at SSRN: https://ssrn.com/abstract=3736401 or http://dx.doi.org/10.2139/ssrn.3736401
This version of the paper has not been formally peer reviewed.

Jenna J. Guthmiller (Contact Author)

University of Chicago - Section of Rheumatology ( email )

United States

Julianna Han

The Scripps Research Institute - Department of Integrative Structural and Computational Biology

10550 North Torrey Pines Road
La Jolla, CA 92037
United States

Lei Li

University of Chicago - Section of Rheumatology

United States

Alec W. Freyn

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Sean T.H. Liu

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Olivia Stovicek

University of Chicago - Section of Rheumatology

United States

Christopher Stamper

University of Chicago - Committee on Immunology ( email )

5841 S Maryland Ave
Chicago, IL 60637
United States

Haley L. Dugan

University of Chicago - Committee on Immunology ( email )

Chicago, IL
United States

Micah E. Tepora

University of Chicago - Section of Rheumatology ( email )

United States

Dalia J. Bitar

University of Chicago - Section of Rheumatology ( email )

United States

Natalie J. Hamel

University of Chicago - Section of Rheumatology ( email )

United States

Siriruk Changrob

University of Chicago - Section of Rheumatology ( email )

United States

Nai-Ying Zheng

University of Chicago - Section of Rheumatology

United States

Min Huang

University of Chicago - Section of Rheumatology

United States

Henry A. Utset

University of Chicago - Section of Rheumatology ( email )

United States

Florian Krammer

Icahn School of Medicine at Mount Sinai - Department of Microbiology ( email )

United States

Raffael Nachbagauer

Icahn School of Medicine at Mount Sinai - Department of Microbiology

United States

Peter Palese

Icahn School of Medicine at Mount Sinai - Department of Microbiology

United States

Andrew B. Ward

The Scripps Research Institute - Department of Integrative Structural and Computational Biology ( email )

10550 North Torrey Pines Road
La Jolla, CA 92037
United States

The Scripps Research Institute - Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery ( email )

La Jolla, CA
United States

The Scripps Research Institute - IAVI Neutralizing Antibody Center ( email )

La Jolla, CA
United States

Patrick C. Wilson

University of Chicago - Section of Rheumatology ( email )

United States

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