Omicron variant Spike-specific antibody binding and Fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines

Author:

Bartsch Yannic C.1ORCID,Tong Xin1,Kang Jaewon1,Avendaño María José2ORCID,Serrano Eileen F.2ORCID,García-Salum Tamara23ORCID,Pardo-Roa Catalina23ORCID,Riquelme Arnoldo345ORCID,Cai Yongfei6ORCID,Renzi Isabella7,Stewart-Jones Guillaume7,Chen Bing6ORCID,Medina Rafael A.238ORCID,Alter Galit1ORCID

Affiliation:

1. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02138, USA.

2. Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.

3. Advanced Interdisciplinary Rehabilitation Register (AIRR)–COVID-19 Working Group, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.

4. Department of Gastroenterology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.

5. Department of Health Sciences, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8331010, Chile.

6. Division of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7. Moderna Inc., Cambridge, MA 02138, USA.

8. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

The Omicron variant of SARS-CoV-2 has been shown to evade neutralizing antibodies elicited by vaccination or infection. Despite the global spread of the Omicron variant, even among highly vaccinated populations, death rates have not increased concomitantly. These data suggest that immune mechanisms beyond antibody-mediated virus neutralization may protect against severe disease. In addition to neutralizing pathogens, antibodies contribute to control and clearance of infections through Fc effector mechanisms. Here, we probed the ability of vaccine-induced antibodies to drive Fc effector activity against the Omicron variant using samples from individuals receiving one of three SARS-CoV-2 vaccines. Despite a substantial loss of IgM, IgA, and IgG binding to the Omicron variant receptor binding domain (RBD) in samples from individuals receiving BNT162b2, mRNA-1273, and CoronaVac vaccines, stable binding was maintained against the full-length Omicron Spike protein. Compromised RBD binding IgG was accompanied by a loss of RBD-specific antibody Fcγ receptor (FcγR) binding in samples from individuals who received the CoronaVac vaccine, but RBD-specific FcγR2a and FcγR3a binding was preserved in recipients of mRNA vaccines. Conversely, Spike protein–specific antibodies exhibited persistent but reduced binding to FcγRs across all three vaccines, although higher binding was observed in samples from recipients of mRNA vaccines. This was associated with preservation of FcγR2a and FcγR3a binding antibodies and maintenance of Spike protein–specific antibody-dependent natural killer cell activation. Thus, despite the loss of Omicron neutralization, vaccine-induced Spike protein–specific antibodies continue to drive Fc effector functions, suggesting a capacity for extraneutralizing antibodies to contribute to disease control.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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