期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：31
DOI：10.1073/pnas.2200592119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron contains extensive mutations and demonstrates enhanced transmission. We used virus-like particles to examine the assembly and neutralization of Omicron and found that Omicron and Delta showed ∼4.6-fold higher assembly and cell entry relative to the ancestral lineage. S and N protein mutations improved assembly and entry while E mutations inhibited assembly. Omicron also escapes neutralization from antisera of vaccinated or convalescent individuals by ∼15-fold. Boosting increased neutralization titers against Omicron and restored neutralization in all subjects compared to one out of eight before boosting. Our results suggest that the rapid spread of Omicron is due to more efficient assembly, cell entry, and escape from antibody neutralization from existing vaccines or previous infection
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant 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 (VLPs), we examined mutations in all four structural proteins and found that Omicron and Delta showed 4.6-fold higher luciferase delivery overall relative to the ancestral B.1 lineage, a property conferred mostly by enhancements in the S and N proteins, while mutations in M and E were mostly detrimental to assembly. Thirty-eight antisera samples from individuals vaccinated with Pfizer/BioNTech, Moderna, or Johnson & Johnson vaccines and convalescent sera from unvaccinated COVID-19 survivors had 15-fold lower efficacy to prevent cell transduction by VLPs containing the Omicron mutations relative to the ancestral B.1 spike protein. A third dose of Pfizer vaccine elicited substantially higher neutralization titers against Omicron, resulting in detectable neutralizing antibodies in eight out of eight subjects compared to one out of eight preboosting. Furthermore, the monoclonal antibody therapeutics casirivimab and imdevimab had robust neutralization activity against B.1 and Delta VLPs but no detectable neutralization of Omicron VLPs, while newly authorized bebtelovimab maintained robust neutralization across variants. Our results suggest that Omicron has similar assembly efficiency and cell entry compared to Delta and that its rapid spread is due mostly to reduced neutralization in sera from previously vaccinated subjects. In addition, most currently available monoclonal antibodies will not be useful in treating Omicron-infected patients with the exception of bebtelovimab.
