SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

Fatima Amanat; Mahima Thapa; Tinting Lei; Shaza M Sayed Ahmed; Daniel C Adelsberg; Juan Manuel Carreño; Shirin Strohmeier; Aaron J Schmitz; Sarah Zafar; Julian Q Zhou; Willemijn Rijnink; Hala Alshammary; Nicholas Borcherding; Ana Gonzalez Reiche; Komal Srivastava; Emilia Mia Sordillo; Harm van Bakel; Personalized Virology Initiative; Jackson S Turner; Goran Bajic; Viviana Simon; Ali H Ellebedy; Florian Krammer

doi:10.1016/j.cell.2021.06.005

SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2

Cell. 2021 Jul 22;184(15):3936-3948.e10. doi: 10.1016/j.cell.2021.06.005. Epub 2021 Jun 8.

Authors

Fatima Amanat¹, Mahima Thapa², Tinting Lei², Shaza M Sayed Ahmed², Daniel C Adelsberg³, Juan Manuel Carreño³, Shirin Strohmeier³, Aaron J Schmitz², Sarah Zafar³, Julian Q Zhou⁴, Willemijn Rijnink³, Hala Alshammary³, Nicholas Borcherding², Ana Gonzalez Reiche⁵, Komal Srivastava³, Emilia Mia Sordillo⁶, Harm van Bakel⁷; Personalized Virology Initiative; Jackson S Turner², Goran Bajic⁸, Viviana Simon⁹, Ali H Ellebedy¹⁰, Florian Krammer¹¹

Collaborators

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
³ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁴ AbCellera Biologics Inc., Vancouver, BC V5Y 0A1, Canada.
⁵ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁶ Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁸ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].
⁹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].
¹⁰ Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO 63110, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: [email protected].
¹¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].

Abstract

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

Keywords: NTD; RBD; SARS-CoV-2; mAbs; mRNA vaccination; plasmablasts; spike.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Amino Acid Substitution
Angiotensin-Converting Enzyme 2 / immunology
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / isolation & purification
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology*
Antibody Formation / immunology
Binding, Competitive
COVID-19 Vaccines / immunology*
Humans
Immunoglobulin G / metabolism
Mutation / genetics
Protein Domains
RNA, Messenger / immunology*
SARS-CoV-2 / immunology*
Somatic Hypermutation, Immunoglobulin / genetics
Spike Glycoprotein, Coronavirus / chemistry*
Spike Glycoprotein, Coronavirus / immunology*
Vaccination*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Immunoglobulin G
RNA, Messenger
Spike Glycoprotein, Coronavirus
ACE2 protein, human
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding