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Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity

The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC(50) in both pseudo and live vi...

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Autores principales: Pande, Kalyan, Hollingsworth, Scott A., Sam, Miranda, Gao, Qinshan, Singh, Sujata, Saha, Anasuya, Vroom, Karin, Ma, Xiaohong Shirley, Brazell, Tres, Gorman, Dan, Chen, Shi-Juan, Raoufi, Fahimeh, Bailly, Marc, Grandy, David, Sathiyamoorthy, Karthik, Zhang, Lan, Thompson, Rob, Cheng, Alan C., Fayadat-Dilman, Laurence, Geierstanger, Bernhard H., Kingsley, Laura J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114490/
https://www.ncbi.nlm.nih.gov/pubmed/35603164
http://dx.doi.org/10.3389/fimmu.2022.864775
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author Pande, Kalyan
Hollingsworth, Scott A.
Sam, Miranda
Gao, Qinshan
Singh, Sujata
Saha, Anasuya
Vroom, Karin
Ma, Xiaohong Shirley
Brazell, Tres
Gorman, Dan
Chen, Shi-Juan
Raoufi, Fahimeh
Bailly, Marc
Grandy, David
Sathiyamoorthy, Karthik
Zhang, Lan
Thompson, Rob
Cheng, Alan C.
Fayadat-Dilman, Laurence
Geierstanger, Bernhard H.
Kingsley, Laura J.
author_facet Pande, Kalyan
Hollingsworth, Scott A.
Sam, Miranda
Gao, Qinshan
Singh, Sujata
Saha, Anasuya
Vroom, Karin
Ma, Xiaohong Shirley
Brazell, Tres
Gorman, Dan
Chen, Shi-Juan
Raoufi, Fahimeh
Bailly, Marc
Grandy, David
Sathiyamoorthy, Karthik
Zhang, Lan
Thompson, Rob
Cheng, Alan C.
Fayadat-Dilman, Laurence
Geierstanger, Bernhard H.
Kingsley, Laura J.
author_sort Pande, Kalyan
collection PubMed
description The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC(50) in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics.
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spelling pubmed-91144902022-05-19 Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity Pande, Kalyan Hollingsworth, Scott A. Sam, Miranda Gao, Qinshan Singh, Sujata Saha, Anasuya Vroom, Karin Ma, Xiaohong Shirley Brazell, Tres Gorman, Dan Chen, Shi-Juan Raoufi, Fahimeh Bailly, Marc Grandy, David Sathiyamoorthy, Karthik Zhang, Lan Thompson, Rob Cheng, Alan C. Fayadat-Dilman, Laurence Geierstanger, Bernhard H. Kingsley, Laura J. Front Immunol Immunology The SARS-CoV-2 pandemic and particularly the emerging variants have deepened the need for widely available therapeutic options. We have demonstrated that hexamer-enhancing mutations in the Fc region of anti-SARS-CoV IgG antibodies lead to a noticeable improvement in IC(50) in both pseudo and live virus neutralization assay compared to parental molecules. We also show that hexamer-enhancing mutants improve C1q binding to target surface. To our knowledge, this is the first time this format has been explored for application in viral neutralization and the studies provide proof-of-concept for the use of hexamer-enhanced IgG1 molecules as potential anti-viral therapeutics. Frontiers Media S.A. 2022-05-04 /pmc/articles/PMC9114490/ /pubmed/35603164 http://dx.doi.org/10.3389/fimmu.2022.864775 Text en Copyright © 2022 Pande, Hollingsworth, Sam, Gao, Singh, Saha, Vroom, Ma, Brazell, Gorman, Chen, Raoufi, Bailly, Grandy, Sathiyamoorthy, Zhang, Thompson, Cheng, Fayadat-Dilman, Geierstanger and Kingsley https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pande, Kalyan
Hollingsworth, Scott A.
Sam, Miranda
Gao, Qinshan
Singh, Sujata
Saha, Anasuya
Vroom, Karin
Ma, Xiaohong Shirley
Brazell, Tres
Gorman, Dan
Chen, Shi-Juan
Raoufi, Fahimeh
Bailly, Marc
Grandy, David
Sathiyamoorthy, Karthik
Zhang, Lan
Thompson, Rob
Cheng, Alan C.
Fayadat-Dilman, Laurence
Geierstanger, Bernhard H.
Kingsley, Laura J.
Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title_full Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title_fullStr Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title_full_unstemmed Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title_short Hexamerization of Anti-SARS CoV IgG1 Antibodies Improves Neutralization Capacity
title_sort hexamerization of anti-sars cov igg1 antibodies improves neutralization capacity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114490/
https://www.ncbi.nlm.nih.gov/pubmed/35603164
http://dx.doi.org/10.3389/fimmu.2022.864775
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