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

Planas, Delphine; Saunders, Nell; Maes, Piet; Guivel‐Benhassine, Florence; Planchais, Cyril; Buchrieser, Julian; Bolland, William-Henry; Porrot, Françoise; Staropoli, Isabelle; Lemoine, Frédéric; Péré, Hélène; Veyer, David; Puech, Julien; Rodary, Julien; Baela, Guy; Dellicour, Simon; Raymenants, Joren; Gorissen, Sarah; Geenen, Caspar; Vanmechelen, Bert; Wawina-Bokalanga, Tony; Martí-Carrerasi, Joan; Cuypers, Lize; Sève, Aymeric; Hocqueloux, Laurent; Prazuck, Thiérry; Rey, F.A.; Simon-Lorrière, Etienne; Bruel, Timothée; Mouquet, Hugo; André, Emmanuel; Schwartz, Olivier

doi:10.1038/d41586-021-03827-2

Cited by 124 publications

(116 citation statements)

References 33 publications

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“…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.…”

Section: Short Communicationsupporting

confidence: 90%

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

Touret

Baronti

Bouzidi

et al. 2022

Preprint

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The emergence and rapid spread of the Omicron variant of SARS-CoV-2, which has more than 30 substitutions in the spike glycoprotein, compromises the efficacy of currently available vaccines and therapeutic antibodies. Using a clinical strain of the Omicron variant, we analyzed the neutralizing power of eight currently used monoclonal antibodies compared to the ancestral B.1 BavPat1 D614G strain. We observed that six of these antibodies have lost their ability to neutralize the Omicron variant. Of the antibodies still having neutralizing activity, Sotrovimab/Vir-7831 shows the smallest reduction in activity, with a factor change of 3.1. Cilgavimab/AZD1061 alone shows a reduction in efficacy of 15.8, resulting in a significant loss of activity for the Evusheld cocktail (42.6 fold reduction) in which the other antibody, Tixagevimab, does not retain significant activity against Omicron. Our results suggest that the clinical efficacy of the initially proposed doses should be rapidly evaluated and the possible need to modify doses or propose combination therapies should be considered.

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Section: Short Communicationsupporting

confidence: 90%

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

Touret

Baronti

Bouzidi

et al. 2022

Preprint

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show abstract

“…Omicron is responsible for the current surge of infections in South Africa, and is becoming globally dominant. With over 30 mutations in the spike protein, a substantial ability to evade the neutralizing antibody response has been described [3][4][5][6] . This associates with greater capacity for reinfection 7 , as well as lower early estimates of vaccine effectiveness against symptomatic disease 8,9 .…”

Section: Main Textmentioning

confidence: 99%

SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron

Keeton

Tincho

Ngomti

et al. 2021

Preprint

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The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron's extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa.

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“…The rapid global spread of the Omicron VOC has been associated with vaccine-breakthrough infections and re-infections 16,17 . Moreover, like previous findings that the Beta VOC compromised vaccine-induced neutralizing antibody (NAb) 12,18,19 , the Omicron VOC has resulted in even worse NAb evasion due to more than 30 alarming mutations in SARS-CoV-2 spike glycoprotein [20][21][22][23] . Considering that current NAb combination for clinical immunotherapy showed significantly reduced activities 21,24 , we sought to search for vaccineinduced broadly neutralizing antibody (bNAbs) among elite vaccinees.…”

Section: Introductionmentioning

confidence: 57%

“…Since Omicron variant escaped from NTD-specific NAbs and majority of known RBDspecific NAbs in the class I, class II, class III and class IV groups 20,21,31 , we sought to determine possible mutations or deletions responsible for antibody resistance for ZCB3 and ZCB11 as compared with the control ZB8. We first constructed and tested a large panel of pseudoviruses carrying individual mutations or deletions found in Omicron variant as compared with those previously found in Alpha, Beta, Gamma and Delta variants (Fig.…”

Section: Naturally Occurred Mutations or Deletions Conferring Antibody Resistancementioning

confidence: 99%

“…VOCs including Omicron and Omicron R346K at comparable high potency in vitro but also protected golden Syrian hamsters against the major circulating Omicron and Delta variants. Till now, few existing NAbs under clinical development have displayed similar neutralization breadth and in vivo potency 20,21 . Since sequence analysis revealed that ZCB11 was a family member of public antibodies with the IGHV1-58 heavy chain and IGKV3-20 light chain, our .…”

Section: It Remains Unclear What Type Of Human Monoclonal Nabs Can Potently Neutralize All Currentmentioning

confidence: 99%

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An elite broadly neutralizing antibody protects SARS-CoV-2 Omicron variant challenge

Zhou

Chan

et al. 2022

Preprint

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The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variant have posted great challenges on the efficacy of current vaccines and antibody immunotherapy. Here, we screened 34 BNT162b2-vaccinees and cloned a public broadly neutralizing antibody (bNAb) ZCB11 from an elite vaccinee. ZCB11 neutralized all authentic SARS-CoV-2 variants of concern (VOCs), including Omicron and OmicronR346K with potent IC50 concentrations of 36.8 and 11.7 ng/mL, respectively. Functional analysis demonstrated that ZCB11 targeted viral receptor-binding domain (RBD) and competed strongly with ZB8, a known RBD-specific class II NAb. Pseudovirus-based mapping of 57 naturally occurred single mutations or deletions revealed that only S371L resulted in 11-fold neutralization resistance, but this phenotype was not observed in the Omicron variant. Furthermore, prophylactic ZCB11 administration protected lung infection against both the circulating pandemic Delta and Omicron variants in golden Syrian hamsters. These results demonstrated that vaccine-induced ZCB11 is a promising bNAb for immunotherapy against pandemic SARS-CoV-2 VOCs.

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

Cited by 124 publications

References 33 publications

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

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

SARS-CoV-2 spike T cell responses induced upon vaccination or infection remain robust against Omicron

An elite broadly neutralizing antibody protects SARS-CoV-2 Omicron variant challenge

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