Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

BioRxiv : the Preprint Server for Biology
Yiska WeisblumPaul D Bieniasz

Abstract

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

Citations

Aug 2, 2020·Nature Reviews. Immunology·Matthew Brown
Sep 10, 2020·Nature·Ewen Callaway
Oct 13, 2020·Nature·Christopher O BarnesPamela J Bjorkman
Dec 3, 2020·Canadian Journal of Microbiology·Raquel RussellBrian L Mark
Feb 25, 2021·Pediatric Hematology and Oncology·Satya Prakash YadavSmita Sarma

Methods Mentioned

BETA
PCR
Illumina sequencing
FACS

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