A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

Aaron J Schmitz; Jackson S Turner; Zhuoming Liu; Julian Q Zhou; Ishmael D Aziati; Rita E Chen; Astha Joshi; Traci L Bricker; Tamarand L Darling; Daniel C Adelsberg; Clara G Altomare; Wafaa B Alsoussi; James Brett Case; Laura A VanBlargan; Tingting Lei; Mahima Thapa; Fatima Amanat; Trushar Jeevan; Thomas Fabrizio; Jane A O'Halloran; Pei-Yong Shi; Rachel M Presti; Richard J Webby; Florian Krammer; Sean P J Whelan; Goran Bajic; Michael S Diamond; Adrianus C M Boon; Ali H Ellebedy

doi:10.1016/j.immuni.2021.08.013

A vaccine-induced public antibody protects against SARS-CoV-2 and emerging variants

Immunity. 2021 Sep 14;54(9):2159-2166.e6. doi: 10.1016/j.immuni.2021.08.013. Epub 2021 Aug 17.

Authors

Aaron J Schmitz¹, Jackson S Turner¹, Zhuoming Liu², Julian Q Zhou¹, Ishmael D Aziati³, Rita E Chen⁴, Astha Joshi³, Traci L Bricker³, Tamarand L Darling³, Daniel C Adelsberg⁵, Clara G Altomare⁵, Wafaa B Alsoussi⁶, James Brett Case³, Laura A VanBlargan³, Tingting Lei¹, Mahima Thapa¹, Fatima Amanat⁷, Trushar Jeevan⁸, Thomas Fabrizio⁸, Jane A O'Halloran³, Pei-Yong Shi⁹, Rachel M Presti¹⁰, Richard J Webby⁸, Florian Krammer⁵, Sean P J Whelan², Goran Bajic⁵, Michael S Diamond¹¹, Adrianus C M Boon¹², Ali H Ellebedy¹³

Affiliations

¹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
² Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
³ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁵ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
⁷ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
⁹ Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
¹⁰ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA.
¹¹ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
¹² Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].
¹³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: [email protected].

Abstract

The emergence of SARS-CoV-2 antigenic variants with increased transmissibility is a public health threat. Some variants show substantial resistance to neutralization by SARS-CoV-2 infection- or vaccination-induced antibodies. Here, we analyzed receptor binding domain-binding monoclonal antibodies derived from SARS-CoV-2 mRNA vaccine-elicited germinal center B cells for neutralizing activity against the WA1/2020 D614G SARS-CoV-2 strain and variants of concern. Of five monoclonal antibodies that potently neutralized the WA1/2020 D614G strain, all retained neutralizing capacity against the B.1.617.2 variant, four also neutralized the B.1.1.7 variant, and only one, 2C08, also neutralized the B.1.351 and B.1.1.28 variants. 2C08 reduced lung viral load and morbidity in hamsters challenged with the WA1/2020 D614G, B.1.351, or B.1.617.2 strains. Clonal analysis identified 2C08-like public clonotypes among B cells responding to SARS-CoV-2 infection or vaccination in 41 out of 181 individuals. Thus, 2C08-like antibodies can be induced by SARS-CoV-2 vaccines and mitigate resistance by circulating variants of concern.

Keywords: B cell; SARS-CoV-2; germinal center; hamster; lymph node; mRNA vaccine; neutralizing antibodies; public clone; receptor binding domain; spike protein.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies, Monoclonal / metabolism*
Antibodies, Neutralizing / metabolism*
Antibodies, Viral / metabolism*
B-Lymphocytes / immunology*
COVID-19 / immunology*
COVID-19 Vaccines / immunology*
Cells, Cultured
Clone Cells
Cricetinae
Disease Models, Animal
Germinal Center / immunology*
Humans
Lung / virology*
Neutralization Tests
SARS-CoV-2 / physiology*
Spike Glycoprotein, Coronavirus / immunology
Vaccination
Viral Load

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

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