A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies.
Nat Commun
; 12(1): 1715, 2021 03 17.
Article
in English
| MEDLINE | ID: covidwho-1139739
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal, Humanized
/
Spike Glycoprotein, Coronavirus
/
Betacoronavirus
/
Epitopes
Type of study:
Randomized controlled trials
Topics:
Vaccines
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Commun
Journal subject:
Biology
/
Science
Year:
2021
Document Type:
Article
Affiliation country:
S41467-021-21968-w
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