The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic

Abstract

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

Acquired neutralizing breadth against SARS-CoV-2 variants including Omicron after three doses of mRNA COVID-19 vaccination and the vaccine efficacy

“…25 There is thus great concern about the Omicron variant's higher transmissibility and immune escapes from COVID-19 vaccines and antibody-based therapies. [26][27][28][29] It has also been demonstrated that vaccine-induced neutralizing antibody responses decrease with increased time post-vaccination. 30,31 To counteract the decline of the neutralizing antibody response over time and the emergence of new variants including Omicron, a third dose of vaccination, which has been called a "booster vaccination," has been approved and administered to individuals who were vaccinated >6 months ago; the booster vaccination has been shown to 6 effectively induce a high titer of neutralizing antibody.…”

Molecular basis of SARS-CoV-2 Omicron variant receptor engagement and antibody evasion and neutralization

“…While for Delta S trimer, our recent work showed the open-transition ratio is 75.3%-24.7%, indicating the conformational masking mechanism may be less effective for the Delta variant 32,36 . This could contribute greatly to the striking immune evasion of the Omicron variant 15,[17][18][19][20][21][22] .…”

“…As the consequence, Omicron has been observed to extensively escape neutralization by previously developed neutralizing monoclonal antibodies (MAbs) or sera from vaccines or convalescent individuals 15,[17][18][19][20][21][22] . Among all of the Omicron S mutations, 15 are present in the receptor-binding domain (RBD) that mediates the virus binding to its host-cell receptorangiotensin-converting enzyme 2 (ACE2) and is also a major target for neutralizing antibodies [23][24][25][26][27] .…”

Rapid and sensitive identification of omicron by variant-specific PCR and nanopore sequencing: paradigm for diagnostics of emerging SARS-CoV-2 variants

“…Recent laboratory studies and epidemiological reports have now confirmed this exceptional combination of high contagiousity and drastic escape from neutralizing antibodies [ 10 – 12 ]. The resistance to neutralization is most likely due to mutations K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y and Y505H, which are located within or close to the epitopes bound by these antibodies [ 13 ].…”