Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera

TLDR

Omicron carries numerous spike mutations that likely diminish recognition by neutralizing antibodies. The study assessed neutralization of Wuhan, Beta, Delta, and Omicron pseudoviruses using sera from 51 participants who received two or three doses of the BNT162b2 mRNA vaccine. Two doses produced >22‑fold lower Omicron neutralization than Wuhan, but a third dose increased Omicron titers 23‑fold to levels comparable to Wuhan after two doses, confirming that a booster is required for effective neutralization and suggesting three doses may protect against Omicron‑mediated COVID‑19.

Abstract

The globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern Omicron (B.1.1.529) has a large number of mutations, especially in the spike protein, indicating that recognition by neutralizing antibodies may be compromised. We tested Wuhan (Wuhan-Hu-1 reference strain), Beta (B.1.351), Delta (B.1.617.2), or Omicron pseudoviruses with sera of 51 participants who received two or three doses of the messenger RNA (mRNA)-based COVID-19 vaccine BNT162b2. After two doses, Omicron-neutralizing titers were reduced >22-fold compared with Wuhan-neutralizing titers. One month after the third vaccine dose, Omicron-neutralizing titers were increased 23-fold relative to their levels after two doses and were similar to levels of Wuhan-neutralizing titers after two doses. The requirement of a third vaccine dose to effectively neutralize Omicron was confirmed with sera from a subset of participants using live SARS-CoV-2. These data suggest that three doses of the mRNA vaccine BNT162b2 may protect against Omicron-mediated COVID-19.