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

TLDR

Neutralizing antibodies from infection or vaccination are expected to be crucial for protection, and passive antibody therapies are promising treatments. The study investigates how SARS‑CoV‑2 may evolve to escape neutralizing antibodies and evaluates whether antibody combinations can prevent this escape. Functional spike variants with RBD and NTD mutations that resist monoclonal antibodies or convalescent plasma were readily selected in a reporter virus, and such resistant variants are already detected at low levels in circulating SARS‑CoV‑2.

Abstract

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.