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

Abstract

From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses resulted in significant global vaccine rollouts that have now significantly lowered Covid-19 hospitalisation and mortality rates in the developed world. Unfortunately, in late 2021, the variant Omicron (B.1.1.529) emerged and it eclipsed the other variants of concern (VOC) in its number of Spike polymorphisms, and its ability to compete with and displacement of the dominant VOC Delta. Herein we accessed the impact of Omicron to humoral neutralisation in vaccinated, convalescent cohorts, in concentrated human IgG from thousands of plasma donors and also alongside many clinically used monoclonal antibodies. Overall, we observed a 17 to 22 fold drop in neutralisation titres across all donors that reached a titre to Omicron. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth but was still reduced by 16-fold. In all therapeutic antibodies tested, significant neutralization was only observed for Sotrovimab, with other monoclonals unable to neutralize B.1.1.529.

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

“…Thus, Omicron totally or partially escapes neutralization by the tested antibodies. Our results are in line with recent preprints 7,8,10 . The neutralization escape correlates with a reduction of binding of the antibodies to the Omicron spike.…”

In vitro evaluation of therapeutic antibodies against a SARS-CoV-2 Omicron B.1.1.529 isolate

“…1), which made it impossible to calculate EC 50 (Table 1). This result is in line with previous EC 50 determination reports (Aggarwal et al, 2021;Cameroni et al, 2021;Planas et al, 2021;VanBlargan et al, 2021;Xie et al, 2021) and with studies exploring the impact of amino-acid mutations in the SARS-CoV-2 spike receptor binding domain (RBD) conferring resistance to monoclonal antibodies (Dong et al, 2021;Starr et al, 2021aStarr et al, , 2021b.…”

Analysis of anti-Omicron neutralizing antibody titers in different vaccinated and unvaccinated convalescent plasma sources

“…With the increase of Omicron seroprevalence in time, polyclonal intravenous immunoglobulins collected from regular donors could become a more standardized alternative to CCP (see Figure 2), but their efficacy to date (at the peak of the vaccinations campaign) is still 16-fold reduced against Omicron compared to wild-type SARS-CoV-2 [14], and such preparations include only IgG and not IgM and IgA, which have powerful SARS-CoV-2 activity.…”

“…Two years into the pandemics, we are back to the starting line for some therapeutic agents. Importantly, Omicron evades most monoclonal antibodies (mAbs) approved to date [5,12-14,20,21] with the lone exception of sotrovimab: nevertheless, as expected for non-cocktail mAb therapies, sotrovimab treatment-emergent immune escape from S:E340K has been shown to be as high as 10% [22,23]. Despite the development of promising oral small-chemical antivirals (molnupiravir and nirmatrelvir), the logistical and economical hurdles for deploying these drugs worldwide will prevent their immediate availability.…”