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

Yiska WeisblumFabian SchmidtFengwen ZhangJustin DaSilvaDaniel PostonJulio C C LorenziFrauke MueckschMagdalena RutkowskaHans-Heinrich HoffmannEleftherios MichailidisChristian GaeblerMarianna AgudeloAlice ChoZijun WangAnna GazumyanMelissa CipollaLarry LuchsingerChristopher D HillyerMarina CaskeyDavide F RobbianiCharles M RiceMichel C NussenzweigTheodora HatziioannouPaul D Bieniasz
Published in: bioRxiv : the preprint server for biology (2020)
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.
Keyphrases
  • sars cov
  • respiratory syndrome coronavirus
  • copy number
  • dengue virus
  • small molecule
  • bone marrow
  • dna methylation
  • zika virus
  • coronavirus disease
  • cell therapy
  • transcription factor
  • current status
  • protein protein