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

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

doi:10.1016/j.chom.2022.07.002

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

Cell Host Microbe. 2022 Sep 14;30(9):1231-1241.e6. doi: 10.1016/j.chom.2022.07.002. Epub 2022 Jul 7.

Affiliations

¹ Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany.
² Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
³ Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁴ Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
⁵ Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and Department of Medicine I, University Medical Center Hamburg-Eppendorf, 20359 Hamburg, Germany.
⁶ Laboratory of Experimental Immunology, Institute of Virology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50931 Cologne, Germany; German Center for Infection Research (DZIF), Partner site Bonn-Cologne, 50937 Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. Electronic address: florian.klein@uk-koeln.de.

Abstract

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.

Keywords: BA.2.12.1; BA.4; BA.5; COVID-19; Omicron; SARS-CoV-2; immune escape; neutralizing antibodies; resistance; sublineages.

MeSH terms

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19*
Humans
Neutralization Tests
SARS-CoV-2*
Spike Glycoprotein, Coronavirus / genetics

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2