Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2

The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze var...

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Main Authors: Anna M. Timofeeva, Sergey E. Sedykh, Tatyana A. Sedykh, Georgy A. Nevinsky
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/11/9/1494
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author Anna M. Timofeeva
Sergey E. Sedykh
Tatyana A. Sedykh
Georgy A. Nevinsky
author_facet Anna M. Timofeeva
Sergey E. Sedykh
Tatyana A. Sedykh
Georgy A. Nevinsky
author_sort Anna M. Timofeeva
collection DOAJ
description The S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca<sup>2+</sup> ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies’ active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19.
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spelling doaj.art-249e930bac8c4abdbeeefb3c4b7f88142023-11-19T13:19:45ZengMDPI AGVaccines2076-393X2023-09-01119149410.3390/vaccines11091494Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2Anna M. Timofeeva0Sergey E. Sedykh1Tatyana A. Sedykh2Georgy A. Nevinsky3SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, RussiaSB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, RussiaSB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, RussiaSB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630090, RussiaThe S-protein is the major antigen of the SARS-CoV-2 virus, against which protective antibodies are generated. The S-protein gene was used in adenoviral vectors and mRNA vaccines against COVID-19. While the primary function of antibodies is to bind to antigens, catalytic antibodies can hydrolyze various substrates, including nucleic acids, proteins, oligopeptides, polysaccharides, and some other molecules. In this study, antibody fractions with affinity for RBD and S-protein (RBD-IgG and S-IgG) were isolated from the blood of COVID-19 patients vaccinated with Sputnik V. The fractions were analyzed for their potential to hydrolyze 18-mer oligopeptides corresponding to linear fragments of the SARS-CoV-2 S-protein. Here, we show that the IgG antibodies hydrolyze six out of nine oligopeptides efficiently, with the antibodies of COVID-19-exposed donors demonstrating the most significant activity. The IgGs of control donors not exposed to SARS-CoV-2 were found to be inactive in oligopeptide hydrolysis. The antibodies of convalescents and vaccinated patients were found to hydrolyze oligopeptides in a wide pH range, with the optimal pH range between 6.5 and 7.5. The hydrolysis of most oligopeptides by RBD-IgG antibodies is inhibited by thiol protease inhibitors, whereas S-IgG active centers generally combine several types of proteolytic activities. Ca<sup>2+</sup> ions increase the catalytic activity of IgG preparations containing metalloprotease-like active centers. Thus, the proteolytic activity of natural antibodies against the SARS-CoV-2 protein is believed to be due to the similarity of catalytic antibodies’ active centers to canonical proteases. This work raises the question of the possible physiological role of proteolytic natural RBD-IgG and S-IgG resulting from vaccination and exposure to COVID-19.https://www.mdpi.com/2076-393X/11/9/1494SARS-CoV-2COVID-19catalytic antibodyIgGautoimmunityS-protein
spellingShingle Anna M. Timofeeva
Sergey E. Sedykh
Tatyana A. Sedykh
Georgy A. Nevinsky
Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
Vaccines
SARS-CoV-2
COVID-19
catalytic antibody
IgG
autoimmunity
S-protein
title Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
title_full Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
title_fullStr Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
title_full_unstemmed Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
title_short Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Recognize and Hydrolyze Oligopeptides Corresponding to the S-Protein of SARS-CoV-2
title_sort natural antibodies produced in vaccinated patients and covid 19 convalescents recognize and hydrolyze oligopeptides corresponding to the s protein of sars cov 2
topic SARS-CoV-2
COVID-19
catalytic antibody
IgG
autoimmunity
S-protein
url https://www.mdpi.com/2076-393X/11/9/1494
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