Congratulations to Henning and Kanika for their studies on different SARS-CoV-2 Omicron sublineages

SARS-CoV-2 Omicron sublineages exhibit distinct antibody escape patterns

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. Importantly, the recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. 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. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.

Neutralisation sensitivity of the SARS-CoV-2 omicron BA.2.75 sublineage

In May, the coronavirus variant BA.2.75 appeared in India for the first time. It is now responsible for around 30 percent of infections locally. To investigate antibody sensitivity of BA.2.75 in comparison with prevalent omicron sublineages, we performed neutralisation assays using pseudoviruses expressing the B.1 (D614G), BA.2, BA.4/5, BA.2.12.1, or BA.2.75 spike proteins. Our results suggest that the mutations in the spike protein of the BA.2.75 sublineage decrease susceptibility to vaccine-induced neutralising activity compared with BA.2, albeit to a lesser extent than the mutations present in BA.4/5. Moreover, BA.2.75 showed an overall higher sensitivity to SARS-CoV-2 neutralising monoclonal antibodies in advanced development, including antibodies currently in clinical use.