A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies.

Nature Communications
Chunyan WangBerend-Jan Bosch

Abstract

The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.

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Citations

May 14, 2021·Nature Structural & Molecular Biology·Maximilian M SauerDavid Veesler
Jul 31, 2021·Frontiers in Immunology·Alice H GrantRobert A Kirken
Aug 5, 2021·Microbiology Spectrum·Sarah E WheelerMichael R Shurin
Jul 3, 2021·Science·Matthew McCallumDavid Veesler
Sep 4, 2021·PLoS Pathogens·Sanjeev KumarAmit Sharma

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Software Mentioned

GraphPad Prism
PEPSCAN
Fortebio Data Analysis
FlowJo

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