Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?

Recently, recombinant monoclonal antibodies (mAbs) of three Ig isotypes (IgG, IgA, and IgM) sharing the same anti-spike protein Fab region were developed; we evaluated their neutralizing abilities using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein and ACE2-transfected Crandell–...

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Main Authors: Yalcin Pisil, Zafer Yazici, Hisatoshi Shida, Tomoyuki Miura
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/10/6/751
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author Yalcin Pisil
Zafer Yazici
Hisatoshi Shida
Tomoyuki Miura
author_facet Yalcin Pisil
Zafer Yazici
Hisatoshi Shida
Tomoyuki Miura
author_sort Yalcin Pisil
collection DOAJ
description Recently, recombinant monoclonal antibodies (mAbs) of three Ig isotypes (IgG, IgA, and IgM) sharing the same anti-spike protein Fab region were developed; we evaluated their neutralizing abilities using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein and ACE2-transfected Crandell–Rees feline kidney cells as the host cell line. Although each of the anti-SARS-CoV-2 mAbs was able to neutralize the spike-coated lentiviruses, IgM and IgA neutralized the viral particles at 225-fold and 125-fold lower concentrations, respectively, than that of IgG. Our finding that the neutralization ability of Igs with the same Fab domain was dramatically higher for IgM and IgA than IgG mAbs suggests a strategy for developing effective and affordable antibody therapies for COVID-19. The efficient neutralization conferred by IgM and IgA mAbs can be explained by their capacity to bind multiple virions. While several IgG mAbs have been approved as therapeutics by the FDA, there are currently no IgM or IgA mAbs available. We suggest that mAbs with multiple antigen-binding sites such as IgM and IgA could be developed as the new generation of therapy.
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spelling doaj.art-e26c8015dc3b4eab9cb33dd95eaf88652023-11-21T23:57:30ZengMDPI AGPathogens2076-08172021-06-0110675110.3390/pathogens10060751Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?Yalcin Pisil0Zafer Yazici1Hisatoshi Shida2Tomoyuki Miura3Laboratory of Primate Model, Research Center for Infectious Diseases, Institute for Frontier Life and Medical Science, Kyoto University, Kyoto 615-8530, JapanDepartment of Virology, Faculty of Veterinary Medicine, 19 Mayis University, Samsun 55270, TurkeyDivision of Molecular Virology, Institute of Immunological Science, Hokkaido University, Hokkaido 060-0808, JapanLaboratory of Primate Model, Research Center for Infectious Diseases, Institute for Frontier Life and Medical Science, Kyoto University, Kyoto 615-8530, JapanRecently, recombinant monoclonal antibodies (mAbs) of three Ig isotypes (IgG, IgA, and IgM) sharing the same anti-spike protein Fab region were developed; we evaluated their neutralizing abilities using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein and ACE2-transfected Crandell–Rees feline kidney cells as the host cell line. Although each of the anti-SARS-CoV-2 mAbs was able to neutralize the spike-coated lentiviruses, IgM and IgA neutralized the viral particles at 225-fold and 125-fold lower concentrations, respectively, than that of IgG. Our finding that the neutralization ability of Igs with the same Fab domain was dramatically higher for IgM and IgA than IgG mAbs suggests a strategy for developing effective and affordable antibody therapies for COVID-19. The efficient neutralization conferred by IgM and IgA mAbs can be explained by their capacity to bind multiple virions. While several IgG mAbs have been approved as therapeutics by the FDA, there are currently no IgM or IgA mAbs available. We suggest that mAbs with multiple antigen-binding sites such as IgM and IgA could be developed as the new generation of therapy.https://www.mdpi.com/2076-0817/10/6/751SARS-CoV-2COVID-19neutralizing antibodyIgGIgMIgA
spellingShingle Yalcin Pisil
Zafer Yazici
Hisatoshi Shida
Tomoyuki Miura
Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
Pathogens
SARS-CoV-2
COVID-19
neutralizing antibody
IgG
IgM
IgA
title Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
title_full Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
title_fullStr Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
title_full_unstemmed Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
title_short Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?
title_sort is sars cov 2 neutralized more effectively by igm and iga than igg having the same fab region
topic SARS-CoV-2
COVID-19
neutralizing antibody
IgG
IgM
IgA
url https://www.mdpi.com/2076-0817/10/6/751
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