Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.
Elife, 2020/10/28;9
Weisblum Y[1], Schmidt F[1], Zhang F[1], DaSilva J[1], Poston D[1], Lorenzi JC[2], Muecksch F[1], Rutkowska M[1], Hoffmann HH[3], Michailidis E[3], Gaebler C[2], Agudelo M[2], Cho A[2], Wang Z[2], Gazumyan A[2], Cipolla M[2], Luchsinger L[4], Hillyer CD[4], Caskey M[2], Robbiani DF[2, 5], Rice CM[3], Nussenzweig MC[2, 6], Hatziioannou T[1], Bieniasz PD[1, 6]
Affiliations
PMID: 33112236
Impact factor: 8.713
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.
Keywords: COVID19; SARS-CoV-2; VSV; antibody; immunology; infectious disease; inflammation; microbiology; virus
MeSH terms
Angiotensin-Converting Enzyme 2; Antibodies, Monoclonal; Antibodies, Neutralizing; Antibodies, Viral; Base Sequence; COVID-19; COVID-19 Vaccines; Epitopes; Genes, Reporter; Humans; Immunization, Passive; Mutation; Neutralization Tests; Protein Domains; Protein Isoforms; Reassortant Viruses; Receptors, Virus; SARS-CoV-2; Selection, Genetic; Spike Glycoprotein, Coronavirus; Vesiculovirus; Virus Replication; COVID-19 Serotherapy
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