The Omicron SARS-CoV-2 virus contains extensive sequence changes relative to the earlier arising B.1, B.1.1 and Delta SARS-CoV-2 variants that have unknown effects on viral infectivity and response to existing
vaccines. Using SARS-CoV-2 virus-like particles (SC2-VLPs), we examined mutations in all four structural
proteins and found that Omicron showed increased infectivity relative to B.1, B.1.1 and similar to Delta, a property conferred by S and N
protein mutations. Thirty-eight
antisera samples from individuals vaccinated with
tozinameran (Pfizer/BioNTech),
elasomeran (Moderna), Johnson & Johnson
vaccines and convalescent sera from unvaccinated
COVID-19 survivors had moderately to dramatically reduced efficacy to prevent cell transduction by VLPs containing the Omicron mutations. The Pfizer/BioNTech and Moderna
vaccine antisera showed strong neutralizing activity against VLPs possessing the ancestral spike
protein (B.1, B.1.1), with 3-fold reduced efficacy against Delta and 15-fold lower neutralization against Omicron VLPs. Johnson & Johnson
antisera showed minimal neutralization of any of the VLPs tested. Furthermore, the
monoclonal antibody therapeutics Casirivimab and Imdevimab had robust neutralization activity against B.1, B.1.1 or Delta VLPs but no detectable neutralization of Omicron VLPs. Our results suggest that Omicron is at least as efficient at assembly and cell entry as Delta, and the antibody response triggered by existing
vaccines or previous
infection, at least prior to boost, will have limited ability to neutralize Omicron. In addition, some currently available
monoclonal antibodies will not be useful in treating Omicron-infected patients.