Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19

Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hy...

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Main Authors: Andrey Matveev, Oleg Pyankov, Yana Khlusevich, Olga Tyazhelkova, Lyudmila Emelyanova, Anna Timofeeva, Andrey Shipovalov, Anton Chechushkov, Natalia Zaitseva, Gleb Kudrov, Gaukhar Yusubalieva, Saule Yussubaliyeva, Oxana Zhukova, Vladimir Baklaushev, Sergey Sedykh, Galina Lifshits, Artem Tikunov, Nina Tikunova
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/13/10799
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author Andrey Matveev
Oleg Pyankov
Yana Khlusevich
Olga Tyazhelkova
Lyudmila Emelyanova
Anna Timofeeva
Andrey Shipovalov
Anton Chechushkov
Natalia Zaitseva
Gleb Kudrov
Gaukhar Yusubalieva
Saule Yussubaliyeva
Oxana Zhukova
Vladimir Baklaushev
Sergey Sedykh
Galina Lifshits
Artem Tikunov
Nina Tikunova
author_facet Andrey Matveev
Oleg Pyankov
Yana Khlusevich
Olga Tyazhelkova
Lyudmila Emelyanova
Anna Timofeeva
Andrey Shipovalov
Anton Chechushkov
Natalia Zaitseva
Gleb Kudrov
Gaukhar Yusubalieva
Saule Yussubaliyeva
Oxana Zhukova
Vladimir Baklaushev
Sergey Sedykh
Galina Lifshits
Artem Tikunov
Nina Tikunova
author_sort Andrey Matveev
collection DOAJ
description Antibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC<sub>50</sub> 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb.
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spelling doaj.art-a78a099836eb43d1a87dd01f600a67652023-11-18T16:43:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-06-0124131079910.3390/ijms241310799Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19Andrey Matveev0Oleg Pyankov1Yana Khlusevich2Olga Tyazhelkova3Lyudmila Emelyanova4Anna Timofeeva5Andrey Shipovalov6Anton Chechushkov7Natalia Zaitseva8Gleb Kudrov9Gaukhar Yusubalieva10Saule Yussubaliyeva11Oxana Zhukova12Vladimir Baklaushev13Sergey Sedykh14Galina Lifshits15Artem Tikunov16Nina Tikunova17Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaState Research Center of Virology and Biotechnology “VECTOR”, Rospotrebnadzor, 630559 Koltsovo, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaState Research Center of Virology and Biotechnology “VECTOR”, Rospotrebnadzor, 630559 Koltsovo, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaLaboratory of Molecular Epidemiology and Biodiversity of Viruses, Research Institute of Virology, Federal Research Center of Fundamental and Translational Medicine, 630117 Novosibirsk, RussiaState Research Center of Virology and Biotechnology “VECTOR”, Rospotrebnadzor, 630559 Koltsovo, RussiaFederal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, RussiaDepartment of General Medical Practice with the Course of Evidence-Based Medicine, Astana Medical University, Nur-Sultan 010000, KazakhstanFederal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, RussiaFederal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, RussiaFaculty of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, RussiaAntibody-dependent enhancement (ADE) has been shown previously for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 infection in vitro. In this study, the first monoclonal antibody (mAb) that causes ADE in a SARS-CoV-2 in vivo model was identified. mAb RS2 against the SARS-CoV-2 S-protein was developed using hybridoma technology. mAb RS2 demonstrated sub-nanomolar affinity and ability to neutralize SARS-CoV-2 infection in vitro with IC<sub>50</sub> 360 ng/mL. In an animal model of SARS-CoV-2 infection, the dose-dependent protective efficacy of mAb RS2 was revealed. However, in post-exposure prophylaxis, the administration of mAb RS2 led to an increase in the viral load in the respiratory tract of animals. Three groups of blood plasma were examined for antibodies competing with mAb RS2: (1) plasmas from vaccinated donors without COVID-19; (2) plasmas from volunteers with mild symptoms of COVID-19; (3) plasmas from patients with severe COVID-19. It was demonstrated that antibodies competing with mAb RS2 were significantly more often recorded in sera from volunteers with severe COVID-19. The results demonstrated for the first time that in animals, SARS-CoV-2 can induce antibody/antibodies that can elicit ADE. Moreover, in the sera of patients with severe COVID-19, there are antibodies competing for the binding of an epitope that is recognized by the ADE-eliciting mAb.https://www.mdpi.com/1422-0067/24/13/10799COVID-19SARS-CoV-2antibody-dependent enhancementmonoclonal antibodyvirus neutralizing antibodyADE
spellingShingle Andrey Matveev
Oleg Pyankov
Yana Khlusevich
Olga Tyazhelkova
Lyudmila Emelyanova
Anna Timofeeva
Andrey Shipovalov
Anton Chechushkov
Natalia Zaitseva
Gleb Kudrov
Gaukhar Yusubalieva
Saule Yussubaliyeva
Oxana Zhukova
Vladimir Baklaushev
Sergey Sedykh
Galina Lifshits
Artem Tikunov
Nina Tikunova
Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
International Journal of Molecular Sciences
COVID-19
SARS-CoV-2
antibody-dependent enhancement
monoclonal antibody
virus neutralizing antibody
ADE
title Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
title_full Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
title_fullStr Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
title_full_unstemmed Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
title_short Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
title_sort antibodies capable of enhancing sars cov 2 infection can circulate in patients with severe covid 19
topic COVID-19
SARS-CoV-2
antibody-dependent enhancement
monoclonal antibody
virus neutralizing antibody
ADE
url https://www.mdpi.com/1422-0067/24/13/10799
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