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

• DOI: 10.1016/j.chom.2022.07.002
• Publication Date: 2022-07-07T12:07:40Z
• Authors: Henning Gruell; Kanika Vanshylla; Michael Korenkov; Pinkus Tober-Lau; Matthias Zehner; Friederike Münn; Hanna Janicki; Max Augustin; Philipp Schommers; Leif Erik Sander; Florian Kurth; Christoph Kreer; Florian Klein
• Keywords: Immune escape; Polyclonal antibodies; Antibody response; 2019-20 coronavirus outbreak

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.