SARS-CoV-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

Abstract

Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in the first world. In late 2021, the Omicron (B.1.1.529) virus variant emerged, with significant genetic differences and clinical effects from other variants of concern (VOC). This variant a demonstrated higher number of polymorphisms in the gene encoding the Spike (S) protein, and there has been displacement of the dominant Delta variant. We assessed the impact of Omicron infection on the ability of: serum from vaccinated and/or previously infected individuals; concentrated human IgG from plasma donors, and licensed monoclonal antibody therapies to neutralise the virus in vitro. There was a 17 to 27-fold reduction in neutralisation titres across all donors who had a detectable neutralising antibody titre to the Omicron variant. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 16-fold. Of all therapeutic antibodies tested, significant neutralisation of the Omicron variant was only observed for Sotrovimab, with other monoclonal antibodies unable to neutralise Omicron in vitro. These results have implications for ongoing therapy of individuals infected with the Omicron variant.

Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2

“…The extensive mutations in the Omicron spike gene mark a dramatic alteration in its antigenicity 15 . Omicron has high transmissibility and high level of immune evasion from WT mRNA vaccine induced immunity, which was reported from various emerging literature 6,14–17 . Omicron’s strong association with reinfection 6 or breakthrough infection 8,12 and its heavily altered antigenicity prompted the idea of developing Omicron-specific mRNA vaccine.…”

Three doses of BNT162b2 vaccine confer neutralising antibody capacity against the SARS-CoV-2 Omicron variant

“…Researchers in Botswana and South Africa identified a new and heavily mutated SARS-CoV-2 variant (B.1.1.529, Omicron) in late November 2021, with 30 amino acid mutations in the Spike protein that are distinct compared to other variants of concern (VOC) Alpha, Beta and Delta 1 . Omicron is characterised by fastspreading in previously vaccinated populations, suggesting Omicron's ability to evade vaccine-induced immunity 2 and therapeutic monoclonal antibody therapy 3 . Several recent studies have indeed confirmed a substantial reduction in neutralising antibody activity against Omicron in small-scaled studies including previously-infected individuals, fully vaccinated individuals, recipients of third booster doses of BNT162b2 or mRNA-1273 and individuals with hybrid immunity (infection followed by vaccination) [4][5][6][7][8][9] .…”

Identifying SARS-CoV-2 Variants of Concern through saliva-based RT-qPCR by targeting recurrent mutation sites

“…Specifically, physicians recommended sotrovimab 37 for COVID-19 treatment, as Delta was the predominant circulating strain at the time. Our assays indicated patient samples were positive for Omicron, which is resistant to monoclonal antibody treatment 38 . This allowed for physicians to pursue other treatment avenues.…”