Elife https://doi.org/10.7554/eLife.61312 (2020)
A major outstanding question in the biology of SARS-CoV-2 is the extent to which the virus will adapt to pressure from the immune system. In eLife, Bieniasz and colleagues use a recombinant chimeric reporter virus that expresses the SARS-CoV-2 spike (S) protein (VSV-SARS-CoV-2) to assess adaptation in the face of neutralizing antibodies — both monoclonal and those found in convalescent plasma. VSV-SARS-CoV-2 lacks a genetic proof reading function, so it is subject to higher mutation rates and therefore allows viral evolution to be tracked in vitro. Under such selective pressure, escape mutations readily appear in the S protein receptor binding domain and confer resistance to antibody neutralization, yet these mutations do not impair ACE2 receptor binding. By interrogating public SARS-CoV-2 databases, the authors found that similar S protein mutations are already circulating in the human population. While the findings have potentially concerning implications for the efficacy of monoclonal antibodies, there was no evidence for complete evasion of convalescent plasma. Therefore, antibody combinations to multiple viral epitopes may limit the impact of SARS-CoV-2 adaptation.
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Fehervari, Z. A shifty target. Nat Immunol 22, 103 (2021). https://doi.org/10.1038/s41590-021-00866-9