Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Published by Elsevier B.V. 2021
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
_version_ 1784580243169738752
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
work_keys_str_mv AT wangyingting sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT allenrobertd sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT kimkenneth sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT shafeenorazizah sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT gonzalezandrewj sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT nguyenmichaeln sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT valentinekristenm sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT caoxia sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT lulucy sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT paichini sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT johnsonsachi sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT kerwinlisa sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT zhouheyue sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT zhangyanliang sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement
AT shrestasujan sarscov2monoclonalantibodieswiththerapeuticpotentialbroadneutralizingactivityandnoevidenceofantibodydependentenhancement