![]() (B) Locations of Omicron-sublineage amino acid changes on the SARS-CoV-2 spike (PDB: 6XR8) with colors as in (A), and RBD and NTD outlined in the bottom models. ![]() (A) Spike amino acid changes in Omicron sublineages relative to Wu01. To this end, we analyzed in detail antibody-mediated neutralization of prevalent and emerging Omicron sublineages (BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5) both on a polyclonal and monoclonal level. Determining their antibody escape properties is therefore of critical importance to effectively guide preventive and therapeutic measures. However, novel sublineages of Omicron are rapidly emerging and associated with increasing numbers of infections ( Tegally et al., 2022 Yamasoba et al., 2022). Most experimental evidence on the resistance of Omicron to antibody-mediated neutralization is limited to analyses of the initial BA.1 strain. Moreover, the spike mutations of Omicron have rendered several therapeutic monoclonal antibodies ineffective ( Gruell et al., 2022a Liu et al., 2022 VanBlargan et al., 2022). Although prolonged vaccine dosing intervals and booster immunizations based on the ancestral Wu01 strain elicit Omicron-neutralizing serum activity, titers against Omicron are considerably lower compared with those against other variants ( Garcia-Beltran et al., 2022 Gruell et al., 2022a Pérez-Then et al., 2022 Schmidt et al., 2022 Wratil et al., 2022 Zhao et al., 2022). Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.ĭespite increasing levels of immunity against SARS-CoV-2 induced by vaccination and infection, the Omicron variant resulted in a global surge of infections that reflects its high transmissibility and immune evasion mediated by a highly mutated spike protein ( Altarawneh et al., 2022 Andrews et al., 2022 Carreño et al., 2022 Cele et al., 2022 Garcia-Beltran et al., 2022 Gruell et al., 2022a Hoffmann et al., 2022 Liu et al., 2022 Madhi et al., 2022 Planas et al., 2022 Schmidt et al., 2022 Tseng et al., 2022 Viana et al., 2022). Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. ![]() By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants.
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