학술논문

Omicron mutations enhance infectivity and reduce antibody neutralization of SARS-CoV-2 virus-like particles
Document Type
article
Source
Proceedings of the National Academy of Sciences of the United States of America. 119(31)
Subject
Prevention
Biotechnology
Pneumonia
Lung
Vaccine Related
Emerging Infectious Diseases
Infectious Diseases
Pneumonia & Influenza
Immunization
Clinical Research
Biodefense
Neurodegenerative
Antibodies
Monoclonal
Humanized
Antibodies
Neutralizing
Antibodies
Viral
COVID-19
Humans
Mutation
SARS-CoV-2
Spike Glycoprotein
Coronavirus
Omicron
virus-like particles
Language
Abstract
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.