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

Abstract

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1,2. It has in the meantime spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the Spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development3, and to antibodies present in 90 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 5 to 31 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies.

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

“…The Omicron variant of SARS-CoV-2, first identified in November 2021 in South Africa and Botswana, has been shown by us 1 and others [2][3][4][5][6][7] to have extensive but incomplete escape from immunity elicited by vaccines and previous infection, with boosted is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

Single-domain antibodies efficiently neutralize SARS-CoV-2 variants of concern, including Omicron variant

“…The activity of most neutralizing antibodies is escaped by the Omicron variant. Several monoclonal antibodies have completely lost their inhibitory activity against Omicron, including bamlanivimab, etesevimab, casirivimab, imdevimab and regdanvimab (18,37). The activity of some previously isolated nanobodies also altered by escape mutations.…”

“…The reduction of neutralization by antibodies is caused by mutations in S glycoprotein, including K417N/T, L452R, T478K, E484K and N501Y substitutions (16,17). Recently appeared Omicron variant has more than 30 mutations in S glycoprotein that provide a considerable escape from neutralization by antibodies (18,19). In this regard, it became necessary to isolate antibodies, the neutralizing activity of which will not be affected due to observed mutations, therefore, these antibodies or their cocktails will retain activity against each of VOCs.…”

A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant

“…Imdevimab, which is delivered in combination with Casirivimab as part of the REGN-CoV cocktail, remains active against Alpha, Beta, and Delta variants. The new Omicron variant, however, appears to be resistant to all four EUA antibodies (Planas et al, 2021;Wilhelm et al, 2021). To address resistant VOCs like Omicron and others that might arise, other programs have focused (Planas et al, 2021) on isolating neutralizing antibodies that target conserved epitopes on the spike protein and are therefore hypothesized to remain active against current and future VOCs.…”

“…The new Omicron variant, however, appears to be resistant to all four EUA antibodies (Planas et al, 2021;Wilhelm et al, 2021). To address resistant VOCs like Omicron and others that might arise, other programs have focused (Planas et al, 2021) on isolating neutralizing antibodies that target conserved epitopes on the spike protein and are therefore hypothesized to remain active against current and future VOCs. A complementary approach is to establish capacity in low-and middle-income countries (LMICs) to isolate monoclonal antibodies from convalescent donors in regions where VOCs are likely to emerge.…”