Antibody cocktail effective against variants of SARS-CoV-2

Abstract 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 neutral...

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Autores principales: Kang-Hao Liang, Pao-Yin Chiang, Shih-Han Ko, Yu-Chi Chou, Ruei-Min Lu, Hsiu-Ting Lin, Wan-Yu Chen, Yi-Ling Lin, Mi-Hua Tao, Jia-Tsrong Jan, Han-Chung Wu
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Publicado: BMC 2021
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spelling oai:doaj.org-article:7e765143995640ccb0b25900e804ab122021-11-28T12:14:17ZAntibody cocktail effective against variants of SARS-CoV-210.1186/s12929-021-00777-91423-0127https://doaj.org/article/7e765143995640ccb0b25900e804ab122021-11-01T00:00:00Zhttps://doi.org/10.1186/s12929-021-00777-9https://doaj.org/toc/1423-0127Abstract 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 IC50 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 PRNT50 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.Kang-Hao LiangPao-Yin ChiangShih-Han KoYu-Chi ChouRuei-Min LuHsiu-Ting LinWan-Yu ChenYi-Ling LinMi-Hua TaoJia-Tsrong JanHan-Chung WuBMCarticleSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Receptor-binding domain (RBD)Neutralizing antibodyCocktail therapyMedicineRENJournal of Biomedical Science, Vol 28, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Receptor-binding domain (RBD)
Neutralizing antibody
Cocktail therapy
Medicine
R
spellingShingle Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Receptor-binding domain (RBD)
Neutralizing antibody
Cocktail therapy
Medicine
R
Kang-Hao Liang
Pao-Yin Chiang
Shih-Han Ko
Yu-Chi Chou
Ruei-Min Lu
Hsiu-Ting Lin
Wan-Yu Chen
Yi-Ling Lin
Mi-Hua Tao
Jia-Tsrong Jan
Han-Chung Wu
Antibody cocktail effective against variants of SARS-CoV-2
description Abstract 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 IC50 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 PRNT50 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.
format article
author Kang-Hao Liang
Pao-Yin Chiang
Shih-Han Ko
Yu-Chi Chou
Ruei-Min Lu
Hsiu-Ting Lin
Wan-Yu Chen
Yi-Ling Lin
Mi-Hua Tao
Jia-Tsrong Jan
Han-Chung Wu
author_facet Kang-Hao Liang
Pao-Yin Chiang
Shih-Han Ko
Yu-Chi Chou
Ruei-Min Lu
Hsiu-Ting Lin
Wan-Yu Chen
Yi-Ling Lin
Mi-Hua Tao
Jia-Tsrong Jan
Han-Chung Wu
author_sort Kang-Hao Liang
title Antibody cocktail effective against variants of SARS-CoV-2
title_short 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_sort antibody cocktail effective against variants of sars-cov-2
publisher BMC
publishDate 2021
url https://doaj.org/article/7e765143995640ccb0b25900e804ab12
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