Anti-SARS-CoV-2 antibodies elicited by COVID-19 mRNA vaccine exhibit a unique glycosylation pattern

Inbal Farkash, Tali Feferman, Noy Cohen-Saban, Yahel Avraham, David Morgenstern, Grace Mayuni, Natasha Barth, Yaniv Lustig, Liron Miller, Dror S. Shouval, Asaf Biber, Ilya Kirgner, Yishai Levin, Rony Dahan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Messenger RNA-based vaccines against COVID-19 induce a robust anti-SARS-CoV-2 antibody response with potent viral neutralization activity. Antibody effector functions are determined by their constant region subclasses and by their glycosylation patterns, but their role in vaccine efficacy is unclear. Moreover, whether vaccination induces antibodies similar to those in patients with COVID-19 remains unknown. We analyze BNT162b2 vaccine-induced IgG subclass distribution and Fc glycosylation patterns and their potential to drive effector function via Fcγ receptors and complement pathways. We identify unique and dynamic pro-inflammatory Fc compositions that are distinct from those in patients with COVID-19 and convalescents. Vaccine-induced anti-Spike IgG is characterized by distinct Fab- and Fc-mediated functions between different age groups and in comparison to antibodies generated during natural viral infection. These data highlight the heterogeneity of Fc responses to SARS-CoV-2 infection and vaccination and suggest that they support long-lasting protection differently.

Original languageEnglish
Article number110114
JournalCell Reports
Volume37
Issue number11
DOIs
StatePublished - 14 Dec 2021

Funding

FundersFunder number
CoronaVirus Weizmann Institute of Science Fund
Dahan lab members Jasmine Balanga
Dwek Institute for Cancer Therapy Research
Ella Herzog
Emerson Collective Cancer Research Fund
Joyce E. Eisenberg Foundation
Max Saad
Mexican Association of Friends of the Weizmann Institute
Miel de Botton
Moross Integrated Cancer Center
NucleAi
Pearl Welinsky Merlo Foundation
Rising Tide Translation Cancer Research Fund
Yeda Research and Development Co.
Yuval Shapir
Israel Cancer Research Fund
Melanoma Research Alliance
Flight Attendant Medical Research Institute
Harry J. Lloyd Charitable Trust
Teva Pharmaceutical Industries
Icahn School of Medicine at Mount Sinai
Mizutani Foundation for Glycoscience
Enoch Foundation
Israel Cancer Association
Israel Science Foundation
Benoziyo Endowment Fund for the Advancement of Science

    Keywords

    • BNT162b2 mRNA vaccine
    • Fc-Glycosylation
    • Fcγ receptors
    • IgG glycosylation
    • IgG-Fc
    • SARS-CoV-2
    • antibodies
    • complement
    • effector function
    • immunity

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