Selective SARS-CoV2 BA.2 escape of antibody Fc/Fc-receptor interactions

Yannic C. Bartsch; Deniz Cizmeci; Jaewon Kang; Hailong Gao; Wei Shi; Abishek Chandrashekar; Ai-ris Y. Collier; Bing Chen; Dan H. Barouch; Galit Alter

iScience (May 2023)

Selective SARS-CoV2 BA.2 escape of antibody Fc/Fc-receptor interactions

Yannic C. Bartsch,
Deniz Cizmeci,
Jaewon Kang,
Hailong Gao,
Wei Shi,
Abishek Chandrashekar,
Ai-ris Y. Collier,
Bing Chen,
Dan H. Barouch,
Galit Alter

Affiliations

Yannic C. Bartsch: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Deniz Cizmeci: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Jaewon Kang: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
Hailong Gao: Division of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Wei Shi: Division of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Abishek Chandrashekar: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Ai-ris Y. Collier: Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Bing Chen: Division of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Dan H. Barouch: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Galit Alter: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 5
p. 106582

Abstract

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Summary: The number of mutations in the omicron (B.1.1.529) BA.1 variant of concern led to an unprecedented evasion of vaccine induced immunity. However, despite rise in global infections, severe disease did not increase proportionally and is likely linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of new sublineage BA.2, which is more transmissible than BA.1 despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine-induced responses. Here, we comprehensively profiled the BNT162b2 vaccine-induced response to several VOCs, including omicron BA.1 and BA.2. While vaccine-induced immune responses were compromised against both omicron sublineages, vaccine-induced antibody isotype titers, and non-neutralizing Fc effector functions were attenuated to the omicron BA.2 spike compared to BA.1. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2, albeit lower than BA.1 responses, potentially contributing to persistent protection against severity of disease.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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Abstract

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