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Authors: Weisblum et al. 

Journal/ Pre-Print:bioXriv 

Key Words:Immunology, Antibodies 

Research Highlights 

  1. Antibody escape Spike protein mutant viruses readily emerge under selection of a single neutralizing antibody, which can be prevented by using a mixture of neutralizing antibodies targeting different epitopes. 

  1. The most potently neutralizing antibodies generated in a COVID-19 convalescent individual contributes only in a minor way to the overall neutralizing antibody response in that same individual. 

Summary

The authors use a replication-competent but proofreading absent VSV-based virus that encodes SARS-CoV-2 spike (S) protein and GFP (Schmidt et al. JEM 2020) to show the emergence of antibody escape mutants under selective pressure of only 1 of 3 potent human anti-SARS-CoV-2 monoclonal antibodies (mAbs)Spike sequence variations of these escape mutants can be found in natural viral populations. Using a mixture of potent neutralizing Abs with non-overlapping binding sites suppresses the emergence of these escape variants.  However, the mAb-resistant mutants were effectively neutralized using convalescent plasma from mAb-respective donors suggesting that these mAbs contribute little to the overall neutralization activity of plasma from the same individual.  

Impact for SARS-CoV2/COVID19 research efforts  

Understanding the immune response to SARS-CoV2/COVID19  

Treatment of SARS-CoV2/COVID19 positive individuals 

Study Type  

  • In vitro study 

Strengths and limitations of the paper 

Novelty: Baum et al. Science 2020 already investigated viral escape mutants 

Standing in the field:Builds upon previous findings (Robbiani et al. 2020; Schmidt et al. 2020, and A. Baum et al. 2020) 

Appropriate statistics:Yes 

Viral model used:Chimeric virus encoding the SARS-CoV-2 spike protein  

Translatability:The findings have important implications for the effectiveness of antibodies as therapeutics but also for long-term protective immunity, especially for re-infection of previously mildly infected individuals  

Main limitations:  

  • All results are obtained using a chimeric virus that only encodes the SARS-CoV-2 spike protein and serial passage experiments in vitro, which is quite an artificial system compared to a natural infection or using the whole virus (however, also quite useful) 

  • A proof-of-concept study whose findings will need to be confirmed in vivo and the clinic