Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera From BNT162b2 or CoronaVac Vaccine Recipients

Abstract

Background The SARS-CoV-2 Omicron variant, designated as a Variant of Concern(VOC) by the World Health Organization, carries numerous spike mutations which have are known to evade neutralizing antibodies elicited by COVID-19 vaccines. A deeper understanding of the susceptibility of Omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment. Methods Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the Omicron, Delta and Beta variants to sera from 25 BNT162b2 and 25 Coronavac vaccine recipients was determined using a live virus microneutralization assay. Results The Omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the Omicron variant HKU691 and HKU344-R346K, respectively, while none of the Coronavac recipients had detectable neutralizing antibody titer against either Omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers(GMT) of the Omicron variant isolates(5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus(229.4), and the GMT of both Omicron variant isolates were significantly lower than those of the Beta and Delta variants. There was no significant difference in the GMT between HKU691 and HKU344-R346K. Conclusions Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or Coronavac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the Omicron variant may be associated with lower COVID-19 vaccine effectiveness.

Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron

“…Preliminary reports suggest that the Omicron variant is highly transmissible, even in fully vaccinated individuals and individuals that received a booster dose [3][4][5] . These results are congruous with recent findings that the Omicron variant is markedly resistant to neutralization by sera not only from convalescent patients, but also from individuals vaccinated with many widely used COVID-19 vaccines [6][7][8][9][10][11] . In addition, the neutralization capacity of monoclonal antibodies (mAbs) in clinical use against COVID-19 is abolished or severely impaired against the Omicron variant [12][13][14] .…”

“…SARS-CoV-2 Omicron that emerged in November 2021 disseminates quickly and may replace Delta as the dominant circulating SARS-CoV-2 variant. Current reports from epidemiology and experimental studies suggest that the Omicron variant can efficiently infect individuals after twodose of vaccination or even after receiving the third booster dose, due to its strong capacity of evading antibody neutralization [6][7][8][9][10][11] . Additional reports have demonstrated that the neutralization capacity of therapeutic monoclonal antibodies against the Omicron variant are also severely impaired, including some with completely abolished activity [12][13][14] .…”

“…A large body of timely reports has revealed that the Omicron variant can robustly escape from neutralization antibodies, allowing it to infect fully vaccinated or even booster vaccinated individuals 3,4,[6][7][8][9][10][11][12][13][14] . Our results in this study suggest that the virus replication fitness of the Omicron variant is severely compromised as a trade-off of escaping from neutralization antibodies.…”

An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants

“…The Omicron RBD carries 15 mutations, most of which localize within the RBM region (Fig. 6a), resulting in reduced vaccine effectiveness and activity loss of many neutralizing antibodies 33,34 . We first measured the binding kinetic of different Nbs against Omicron RBD by BLI.…”

A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron

“…[3][4][5][6] The recently detected Omicron (B.1.1.529) variant, which possesses at least 30 amino acid mutations in S alone, 7 is particularly concerning, as early reports show clear reductions in the efficacy of current therapeutics, including those monoclonal antibody cocktails with Emergency Use Authorization, as well as the commonly used two-dose mRNA vaccine regimens. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] SARS-CoV-2 escape mutations in the RBD presents a particular risk for recently developed neutralizing antibody therapeutics and endangers ongoing public health responses, thus underscoring the need for new therapeutic approaches, such as multivalent antibodies, which have recently been shown to potentiate SARS-CoV-2 neutralization and reduce immune escape when compared to monovalent antibodies. [22][23][24][25][26] Because the Delta and Omicron variants account for 99.7% of cases in the United States (as of December 25, 2021 27 ), a bispecific antibody capable of binding and neutralizing both variants would represent a therapeutic and public health advantage over currently available treatment modalities.…”