SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

Anass Abbad; Temima Yellin; Gagandeep Singh; Miriam Fried; Ariel Raskin; Johnstone Tcheou; Brian Monahan; Charles Gleason; PARIS Study Group; Viviana Simon; Juan Manuel Carreño; Florian Krammer

doi:10.1016/j.xcrm.2024.101474

SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

Cell Rep Med. 2024 Mar 19;5(3):101474. doi: 10.1016/j.xcrm.2024.101474.

Collaborators

PARIS Study Group:
Dalles Andre, Maria C Bermúdez-González, Dominika Bielak, Gianna Cai, Christian Cognigni, Yuexing Chen, Hyun Min Kang, Giulio Kleiner, Neko Lyttle, Jacob Mauldin, Sara Morris, Jessica Nardulli, Annika Oostenink, Ashley-Beathrese Salimbangon, Komal Srivastava, Leeba Sullivan, Morgan Van Kesteren

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: jm.carreno@mssm.edu.
⁴ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria. Electronic address: florian.krammer@mssm.edu.

Abstract

Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe the potency and breadth of neutralizing and binding antibody responses against a large panel of variants following an Omicron BA.1 or BA.2 breakthrough infection in a heterogeneous cohort of individuals with diverse exposure histories. Both BA.1 and BA.2 breakthrough infections significantly boost antibody levels and broaden antibody reactivity. However, this broader immunity induced by BA.1 and BA.2 breakthrough infections does not neutralize Omicron BQ and XBB subvariants efficiently. While these subvariants are not neutralized well by post-breakthrough sera, suggesting escape, binding non-neutralizing antibody responses are sustained. In summary, our data suggest that while BA.1 and BA.2 breakthrough infections broaden the immune response to SARS-CoV-2 spike, the induced neutralizing antibody response is still outpaced by viral evolution.

Keywords: Omicron; SARS-CoV-2; antibody breadth; breakthrough infection; immune escape; neutralizing antibodies.

MeSH terms

Antibodies, Neutralizing
Antibody Formation*
Breakthrough Infections
COVID-19*
Humans
SARS-CoV-2

Substances

Antibodies, Neutralizing