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Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2
Monoclonal antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518701/ https://www.ncbi.nlm.nih.gov/pubmed/36189212 http://dx.doi.org/10.3389/fimmu.2022.980435 |
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author | Ji, Yun Zhang, Qi Cheng, Lin Ge, Jiwan Wang, Ruoke Fang, Mengqi Mucker, Eric M. Chen, Peng Ma, Ji Zhang, Rui Li, Chunming Hammond, Holly Baracco, Lauren Holbrook, Michael Frieman, Matthew Zhang, Zheng Wang, Xinquan Hooper, Jay W. Zhang, Linqi Zhu, Qing |
author_facet | Ji, Yun Zhang, Qi Cheng, Lin Ge, Jiwan Wang, Ruoke Fang, Mengqi Mucker, Eric M. Chen, Peng Ma, Ji Zhang, Rui Li, Chunming Hammond, Holly Baracco, Lauren Holbrook, Michael Frieman, Matthew Zhang, Zheng Wang, Xinquan Hooper, Jay W. Zhang, Linqi Zhu, Qing |
author_sort | Ji, Yun |
collection | PubMed |
description | Monoclonal antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting mAb by regulatory authority. However, the continuous virus evolution requires diverse mAb options to combat variants. Here we describe two fully human mAbs, amubarvimab (BRII-196) and romlusevimab (BRII-198) that bind to non-competing epitopes on the receptor binding domain (RBD) of spike protein and effectively neutralize SARS-CoV-2 variants. A YTE modification was introduced to the fragment crystallizable (Fc) region of both mAbs to prolong serum half-life and reduce effector function. The amubarvimab and romlusevimab combination retained activity against most mutations associated with reduced susceptibility to previously authorized mAbs and against variants containing amino acid substitutions in their epitope regions. Consistently, the combination of amubarvimab and romlusevimab effectively neutralized a wide range of viruses including most variants of concern and interest in vitro. In a Syrian golden hamster model of SARS-CoV-2 infection, animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic. |
format | Online Article Text |
id | pubmed-9518701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95187012022-09-29 Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 Ji, Yun Zhang, Qi Cheng, Lin Ge, Jiwan Wang, Ruoke Fang, Mengqi Mucker, Eric M. Chen, Peng Ma, Ji Zhang, Rui Li, Chunming Hammond, Holly Baracco, Lauren Holbrook, Michael Frieman, Matthew Zhang, Zheng Wang, Xinquan Hooper, Jay W. Zhang, Linqi Zhu, Qing Front Immunol Immunology Monoclonal antibodies (mAbs) targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have demonstrated clinical efficacy in preventing or treating coronavirus disease 2019 (COVID-19), resulting in the emergency use authorization (EUA) for several SARS-CoV-2 targeting mAb by regulatory authority. However, the continuous virus evolution requires diverse mAb options to combat variants. Here we describe two fully human mAbs, amubarvimab (BRII-196) and romlusevimab (BRII-198) that bind to non-competing epitopes on the receptor binding domain (RBD) of spike protein and effectively neutralize SARS-CoV-2 variants. A YTE modification was introduced to the fragment crystallizable (Fc) region of both mAbs to prolong serum half-life and reduce effector function. The amubarvimab and romlusevimab combination retained activity against most mutations associated with reduced susceptibility to previously authorized mAbs and against variants containing amino acid substitutions in their epitope regions. Consistently, the combination of amubarvimab and romlusevimab effectively neutralized a wide range of viruses including most variants of concern and interest in vitro. In a Syrian golden hamster model of SARS-CoV-2 infection, animals receiving combination of amubarvimab and romlusevimab either pre- or post-infection demonstrated less weight loss, significantly decreased viral load in the lungs, and reduced lung pathology compared to controls. These preclinical findings support their development as an antibody cocktail therapeutic option against COVID-19 in the clinic. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9518701/ /pubmed/36189212 http://dx.doi.org/10.3389/fimmu.2022.980435 Text en Copyright © 2022 Ji, Zhang, Cheng, Ge, Wang, Fang, Mucker, Chen, Ma, Zhang, Li, Hammond, Baracco, Holbrook, Frieman, Zhang, Wang, Hooper, Zhang and Zhu 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 Ji, Yun Zhang, Qi Cheng, Lin Ge, Jiwan Wang, Ruoke Fang, Mengqi Mucker, Eric M. Chen, Peng Ma, Ji Zhang, Rui Li, Chunming Hammond, Holly Baracco, Lauren Holbrook, Michael Frieman, Matthew Zhang, Zheng Wang, Xinquan Hooper, Jay W. Zhang, Linqi Zhu, Qing Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title | Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title_full | Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title_fullStr | Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title_full_unstemmed | Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title_short | Preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against SARS-CoV-2 |
title_sort | preclinical characterization of amubarvimab and romlusevimab, a pair of non-competing neutralizing monoclonal antibody cocktail, against sars-cov-2 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518701/ https://www.ncbi.nlm.nih.gov/pubmed/36189212 http://dx.doi.org/10.3389/fimmu.2022.980435 |
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