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Antibody cocktail effective against variants of SARS-CoV-2

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing an...

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Autores principales: Liang, Kang-Hao, Chiang, Pao-Yin, Ko, Shih-Han, Chou, Yu-Chi, Lu, Ruei-Min, Lin, Hsiu-Ting, Chen, Wan-Yu, Lin, Yi-Ling, Tao, Mi-Hua, Jan, Jia-Tsrong, Wu, Han-Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609252/
https://www.ncbi.nlm.nih.gov/pubmed/34814920
http://dx.doi.org/10.1186/s12929-021-00777-9
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author Liang, Kang-Hao
Chiang, Pao-Yin
Ko, Shih-Han
Chou, Yu-Chi
Lu, Ruei-Min
Lin, Hsiu-Ting
Chen, Wan-Yu
Lin, Yi-Ling
Tao, Mi-Hua
Jan, Jia-Tsrong
Wu, Han-Chung
author_facet Liang, Kang-Hao
Chiang, Pao-Yin
Ko, Shih-Han
Chou, Yu-Chi
Lu, Ruei-Min
Lin, Hsiu-Ting
Chen, Wan-Yu
Lin, Yi-Ling
Tao, Mi-Hua
Jan, Jia-Tsrong
Wu, Han-Chung
author_sort Liang, Kang-Hao
collection PubMed
description BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies. METHODS: We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments. RESULTS: The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC(50) values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT(50) values 4.93–37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters. CONCLUSIONS: The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta.
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spelling pubmed-86092522021-11-23 Antibody cocktail effective against variants of SARS-CoV-2 Liang, Kang-Hao Chiang, Pao-Yin Ko, Shih-Han Chou, Yu-Chi Lu, Ruei-Min Lin, Hsiu-Ting Chen, Wan-Yu Lin, Yi-Ling Tao, Mi-Hua Jan, Jia-Tsrong Wu, Han-Chung J Biomed Sci Research BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus with a high mutation rate. Importantly, several currently circulating SARS-CoV-2 variants are associated with loss of efficacy for both vaccines and neutralizing antibodies. METHODS: We analyzed the binding activity of six highly potent antibodies to the spike proteins of SARS-CoV-2 variants, assessed their neutralizing abilities with pseudovirus and authentic SARS-CoV-2 variants and evaluate efficacy of antibody cocktail in Delta SARS-CoV-2-infected hamster models as prophylactic and post-infection treatments. RESULTS: The tested RBD-chAbs, except RBD-chAb-25, maintained binding ability to spike proteins from SARS-CoV-2 variants. However, only RBD-chAb-45 and -51 retained neutralizing activities; RBD-chAb-1, -15, -25 and -28 exhibited diminished neutralization for all SARS-CoV-2 variants. Notably, several cocktails of our antibodies showed low IC(50) values (3.35–27.06 ng/ml) against the SARS-CoV-2 variant pseudoviruses including United Kingdom variant B.1.1.7 (Alpha), South Africa variant B.1.351 (Beta), Brazil variant P1 (Gamma), California variant B.1.429 (Epsilon), New York variant B.1.526 (Iota), and India variants, B.1.617.1 (Kappa) and B.1.617.2 (Delta). RBD-chAb-45, and -51 showed PRNT(50) values 4.93–37.54 ng/ml when used as single treatments or in combination with RBD-chAb-15 or -28, according to plaque assays with authentic Alpha, Gamma and Delta SARS-CoV-2 variants. Furthermore, the antibody cocktail of RBD-chAb-15 and -45 exhibited potent prophylactic and therapeutic effects in Delta SARS-CoV-2 variant-infected hamsters. CONCLUSIONS: The cocktail of RBD-chAbs exhibited potent neutralizing activities against SARS-CoV-2 variants. These antibody cocktails are highly promising candidate tools for controlling new SARS-CoV-2 variants, including Delta. BioMed Central 2021-11-23 /pmc/articles/PMC8609252/ /pubmed/34814920 http://dx.doi.org/10.1186/s12929-021-00777-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liang, Kang-Hao
Chiang, Pao-Yin
Ko, Shih-Han
Chou, Yu-Chi
Lu, Ruei-Min
Lin, Hsiu-Ting
Chen, Wan-Yu
Lin, Yi-Ling
Tao, Mi-Hua
Jan, Jia-Tsrong
Wu, Han-Chung
Antibody cocktail effective against variants of SARS-CoV-2
title Antibody cocktail effective against variants of SARS-CoV-2
title_full Antibody cocktail effective against variants of SARS-CoV-2
title_fullStr Antibody cocktail effective against variants of SARS-CoV-2
title_full_unstemmed Antibody cocktail effective against variants of SARS-CoV-2
title_short Antibody cocktail effective against variants of SARS-CoV-2
title_sort antibody cocktail effective against variants of sars-cov-2
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8609252/
https://www.ncbi.nlm.nih.gov/pubmed/34814920
http://dx.doi.org/10.1186/s12929-021-00777-9
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