Abstract
The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.
Highlights
Most approved coronavirus disease 2019 (COVID-19) vaccines are based on transient expression of the viral spike (S) glycoprotein to induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-directed immunity[1]
Compared with previously described variant of concern (VOC), the Omicron variant is notable for its high number of non-synonymous mutations relative to the ancestral Wu01 strain of SARS-CoV-2
The majority of these mutations are located in the viral spike glycoprotein and include critical epitopes for SARS-CoV-2-neutralizing antibodies in the N-terminal domain and the receptor-binding domain (RBD)
Summary
Most approved coronavirus disease 2019 (COVID-19) vaccines are based on transient expression of the viral spike (S) glycoprotein (derived from the Wu01 strain) to induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-directed immunity[1]. To determine the susceptibility of the Omicron variant to vaccine-induced serum activity, we analyzed samples obtained from 30 individuals with no evidence of prior infection[8].
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