SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Abstract

On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants

“…5a). The IgG endpoint GMTs reached ~2.1×10 4 (20 µg), ~1.6×10 4 (100 µg dose) and ~7×10 3 (500 µg dose) for circRNA RBD vaccines, while circRNA Ctrl or PBS-immunized rhesus macaques failed to induce RBD-specific antibodies (Fig. 5b).…”

“…The circRNA RBD-Omicron vaccine could induce Omicron Spike-specific antibodies with the endpoint GMTs of ~4.7×10 4 for 5 µg dose and ~2.2×10 5 for 10 µg dose (Fig. 4d), yielding evident neutralizing activities against Omicron with the NT50 of ~2.5×10 3 for the 5 µg dose and ~8.6×10 3 for the 10 µg dose (Fig. 4e).…”

“…the next dominant strain. Omicron carries over 30 mutations on the Spike protein, 15 of which are located in the receptor-binding domain (RBD) 3 , resulting in a significant decrease in the effectiveness of prior neutralizing antibodies [4][5][6][7][8] . This poses a severe challenge to the efficacy of current vaccines, highlighting the urgent need to develop effective vaccines against such fastspreading variants.…”

Viral Load in COVID-19 Patients: Implications for Prognosis and Vaccine Efficacy in the Context of Emerging SARS-CoV-2 Variants

“…This variant was detected on 6 continents within a month of its initial discovery and has raised concerns around the world. The omicron VOC is a heavily mutated SARS-CoV-2, with 30 amino acid substitutions, deletion of six residues, and insertion of three residues in the spike protein, mostly concentrated around the receptor binding motif (88). Among the mutations, an insertion (ins214EPE) in spike that was not been previously observed in other SARS-CoV-2 variants (140).…”

“…These findings suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness. Regarding the effect of neutralizing activity against monoclonal antibody-based therapies, recent findings showed that the omicron VOC substantially reduces neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development (88). The impact of omicron on disease severity, death and hospitalization is yet to be answered.…”