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SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement
Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic,...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier B.V.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498781/ https://www.ncbi.nlm.nih.gov/pubmed/34634289 http://dx.doi.org/10.1016/j.antiviral.2021.105185 |
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author | Wang, Ying-Ting Allen, Robert D. Kim, Kenneth Shafee, Norazizah Gonzalez, Andrew J. Nguyen, Michael N. Valentine, Kristen M. Cao, Xia Lu, Lucy Pai, Chin-I Johnson, Sachi Kerwin, Lisa Zhou, Heyue Zhang, Yanliang Shresta, Sujan |
author_facet | Wang, Ying-Ting Allen, Robert D. Kim, Kenneth Shafee, Norazizah Gonzalez, Andrew J. Nguyen, Michael N. Valentine, Kristen M. Cao, Xia Lu, Lucy Pai, Chin-I Johnson, Sachi Kerwin, Lisa Zhou, Heyue Zhang, Yanliang Shresta, Sujan |
author_sort | Wang, Ying-Ting |
collection | PubMed |
description | Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic, concern has been raised about the potential for Fcγ receptor-mediated antibody-dependent enhancement (ADE) of infection. In this study, plaque reduction neutralization assays demonstrated that mAb 1741-LALA neutralizes SARS-CoV-2 strains B.1.351, D614 and D614G. MAbs S1D2-hIgG1 and S1D2-LALA mutant (STI-1499-LALA) did not neutralize B.1.351, but did neutralize SARS-CoV-2 strains D614 and D614G. LALA mutations did not result in substantial differences in neutralizing abilities between clones S1D2-hIgG1 vs STI-1499-LALA. S1D2-hIgG1, STI-1499-LALA, and convalescent plasma showed minimal ability to induce ADE in human blood monocyte-derived macrophages. Further, no differences in pharmacokinetic clearance of S1D2-hIgG1 vs STI-1499-LALA were observed in mice expressing human FcRn. These findings confirm that SARS-CoV-2 has already escaped some mAbs, and identify a mAb candidate that may neutralize multiple SARS-CoV-2 variants. They also suggest that risk of ADE in macrophages may be low with SARS-CoV-2 D614, and LALA Fc change impacts neither viral neutralization nor Ab clearance. |
format | Online Article Text |
id | pubmed-8498781 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84987812021-10-08 SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement Wang, Ying-Ting Allen, Robert D. Kim, Kenneth Shafee, Norazizah Gonzalez, Andrew J. Nguyen, Michael N. Valentine, Kristen M. Cao, Xia Lu, Lucy Pai, Chin-I Johnson, Sachi Kerwin, Lisa Zhou, Heyue Zhang, Yanliang Shresta, Sujan Antiviral Res Article Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic, concern has been raised about the potential for Fcγ receptor-mediated antibody-dependent enhancement (ADE) of infection. In this study, plaque reduction neutralization assays demonstrated that mAb 1741-LALA neutralizes SARS-CoV-2 strains B.1.351, D614 and D614G. MAbs S1D2-hIgG1 and S1D2-LALA mutant (STI-1499-LALA) did not neutralize B.1.351, but did neutralize SARS-CoV-2 strains D614 and D614G. LALA mutations did not result in substantial differences in neutralizing abilities between clones S1D2-hIgG1 vs STI-1499-LALA. S1D2-hIgG1, STI-1499-LALA, and convalescent plasma showed minimal ability to induce ADE in human blood monocyte-derived macrophages. Further, no differences in pharmacokinetic clearance of S1D2-hIgG1 vs STI-1499-LALA were observed in mice expressing human FcRn. These findings confirm that SARS-CoV-2 has already escaped some mAbs, and identify a mAb candidate that may neutralize multiple SARS-CoV-2 variants. They also suggest that risk of ADE in macrophages may be low with SARS-CoV-2 D614, and LALA Fc change impacts neither viral neutralization nor Ab clearance. Published by Elsevier B.V. 2021-11 2021-10-08 /pmc/articles/PMC8498781/ /pubmed/34634289 http://dx.doi.org/10.1016/j.antiviral.2021.105185 Text en © 2021 Published by Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Wang, Ying-Ting Allen, Robert D. Kim, Kenneth Shafee, Norazizah Gonzalez, Andrew J. Nguyen, Michael N. Valentine, Kristen M. Cao, Xia Lu, Lucy Pai, Chin-I Johnson, Sachi Kerwin, Lisa Zhou, Heyue Zhang, Yanliang Shresta, Sujan SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title | SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title_full | SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title_fullStr | SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title_full_unstemmed | SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title_short | SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement |
title_sort | sars-cov-2 monoclonal antibodies with therapeutic potential: broad neutralizing activity and no evidence of antibody-dependent enhancement |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498781/ https://www.ncbi.nlm.nih.gov/pubmed/34634289 http://dx.doi.org/10.1016/j.antiviral.2021.105185 |
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