Broad sarbecovirus neutralizing antibodies define a key site of vulnerability on the SARS-CoV-2 spike protein

BioRxiv : the Preprint Server for Biology
Anna Z WecLaura M Walker

Abstract

Broadly protective vaccines against known and pre-emergent coronaviruses are urgently needed. Critical to their development is a deeper understanding of cross-neutralizing antibody responses induced by natural human coronavirus (HCoV) infections. Here, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a new target for the rational design of pan-sarbecovirus vaccines.

Citations

Oct 21, 2020·Science Translational Medicine·Barton F HaynesAnn Arvin
Nov 11, 2020·Molecular Medicine·Betty DiamondYousef Al Abed
Jan 5, 2021·Frontiers in Pharmacology·Bruno Silva AndradeVasco Ariston de Carvalho Azevedo
Feb 6, 2021·Scientific Reports·Inga SzurgotPeter Liljeström
May 5, 2021·Expert Opinion on Drug Delivery·Miguel Pereira-SilvaAna Cláudia Santos

Methods Mentioned

BETA
blood draw
biolayer interferometry
flow cytometry
electron microscopy

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