Abstract
Omicron was designated by the WHO as a VOC on 26 November 2021, only 4 days after its sequence was first submitted. However, the impact of Omicron on current antibodies and vaccines remains unknown and evaluations are still a few weeks away. We analysed the mutations in the Omicron variant against epitopes. In our database, 132 epitopes of the 120 antibodies are classified into five groups, namely NTD, RBD-1, RBD-2, RBD-3, and RBD-4. The Omicron mutations impact all epitopes in NTD, RBD-1, RBD-2, and RBD-3, with no antibody epitopes spared by these mutations. Only four out of 120 antibodies may confer full resistance to mutations in the Omicron spike, since all antibodies in these three groups contain one or more epitopes that are affected by these mutations. Of all antibodies under EUA, the neutralisation potential of Etesevimab, Bamlanivimab, Casirivimab, Imdevima, Cilgavimab, Tixagevimab, Sotrovimab, and Regdanvimab might be dampened to varying degrees. Our analysis suggests the impact of Omicron on current therapeutic antibodies by the Omicron spike mutations may also apply to current COVID-19 vaccines.
Highlights
During the current Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) has been tracking SARS-CoV-2 variants in terms of variants of concern (VOCs), variants of interest (VOIs), or variants under monitoring (VUMs) [1]
Our analysis shows that the Omicron mutations impact all epitopes in N-terminal domain (NTD), receptor binding domain (RBD)-1, RBD-2, and RBD-3, with no antibodybinding sites spared by these mutations
The monoclonal antibody epitopes can be classified into five antigenic groups: NTD [4], RBD-1, RBD-2, RBD-3, and RBD-4 [5] (Figure 1A–E)
Summary
During the current Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the World Health Organization (WHO) has been tracking SARS-CoV-2 variants in terms of variants of concern (VOCs), variants of interest (VOIs), or variants under monitoring (VUMs) [1]. The urgent action was prompted by the identification of an unusually large number of mutations in the Omicron spike, which includes 10 mutations in the N-terminal domain (NTD) and 15 mutations in the receptor binding domain (RBD) [3]. While such mutation numbers delayed the validation of impact on therapeutic antibodies and vaccines. Past studies have isolated hundreds of antibodies against the SARS-CoV-2 spike protein for analysing epitopes or developing therapeutic drugs. This allows the identification of the precise structures of antigen-antibody complexes. Since the spike protein in vaccines approved shares an identical structural basis for generating the above-mentioned antibodies, it is urgent to analyse the impact of all mutations in the Omicron spike on both vaccines and therapeutic antibodies
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