Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2

Author:

Klingler Jéromine12,Weiss Svenja12,Itri Vincenza1,Liu Xiaomei12,Oguntuyo Kasopefoluwa Y3,Stevens Christian3,Ikegame Satoshi3,Hung Chuan-Tien3,Enyindah-Asonye Gospel1,Amanat Fatima34,Baine Ian5,Arinsburg Suzanne5,Bandres Juan C2,Kojic Erna Milunka6,Stoever Jonathan7,Jurczyszak Denise34,Bermudez-Gonzalez Maria3,Nádas Arthur8,Liu Sean13,Lee Benhur3,Zolla-Pazner Susan13,Hioe Catarina E123ORCID

Affiliation:

1. Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2. James J. Peters VA Medical Center, Bronx, New York, USA

3. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

4. Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA

5. Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

6. Division of Infectious Diseases, Department of Medicine, Mount Sinai West and Morningside, New York, USA

7. Pulmonary and Critical Care Medicine, Mount Sinai West, New York, USA

8. Department of Environment Medicine, NYU School of Medicine, New York, New York, USA

Abstract

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin isotypes capable of blocking infection. Methods We studied spike- and RBD-specific immunoglobulin isotypes in convalescent and acute plasma/serum samples using a multiplex bead assay. We also determined virus neutralization activities in plasma and serum samples, and purified immunoglobulin fractions using a vesicular stomatitis pseudovirus assay. Results Spike- and RBD-specific immunoglobulin (Ig) M, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions’ neutralization potency. IgA also exhibited neutralizing activity, but with lower potency. Conclusion IgG, IgM, and IgA are critical components of convalescent plasma used for treatment of coronavirus disease 2019 (COVID-19).

Funder

U.S. Department of Veterans Affairs

National Institutes of Health

Viral-Host Pathogenesis Training

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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