Novel B-Cell Epitopes of Non-Neutralizing Antibodies in the Receptor-Binding Domain of the SARS-CoV-2 S-Protein with Different Effects on the Severity of COVID-19
Matveev A.L. Pyankov O.V. Khlusevich Y.A. Tyazhelkova O.V. Emelyanova L.A. Timofeeva A.M. Shipovalov A.V. Chechushkov A.V. Zaitseva N.S. Kudrov G.A. Yusubalieva G.M. Yussubaliyeva S.M. Zhukova O.A. Tikunov A.Y. Baklaushev V.P. Sedykh S.E. Lifshits G.I. Tikunova N.V.
September 2023
Biochemistry (Moscow)
2023#88Issue 91205 - 1214 pp.
Abstract: Antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (RBD S-protein) contribute significantly to the humoral immune response during coronavirus infection (COVID-19) and after vaccination. The main focus of the studies of the RBD epitope composition is usually concentrated on the epitopes recognized by the virus-neutralizing antibodies. The role of antibodies that bind to RBD but do not neutralize SARS-CoV-2 remains unclear. In this study, immunochemical properties of the two mouse monoclonal antibodies (mAbs), RS17 and S11, against the RBD were examined. Both mAbs exhibited high affinity to RBD, but they did not neutralize the virus. The epitopes of these mAbs were mapped using phage display: the epitope recognized by the mAb RS17 is located at the N-terminal site of RBD (348-SVYAVNRKRIS-358); the mAb S11 epitope is inside the receptor-binding motif of RBD (452-YRLFRKSN-459). Three groups of sera were tested for presence of antibodies competing with the non-neutralizing mAbs S11 and RS17: (i) sera from the vaccinated healthy volunteers without history of COVID-19; (ii) sera from the persons who had a mild form of COVID-19; (iii) sera from the persons who had severe COVID-19. Antibodies competing with the mAb S11 were found in each group of sera with equal frequency, whereas presence of the antibodies competing with the mAb RS17 in the sera was significantly more frequent in the group of sera obtained from the patients recovered from severe COVID-19 indicating that such antibodies are associated with the severity of COVID-19. In conclusion, despite the clear significance of anti-RBD antibodies in the effective immune response against SARS-CoV-2, it is important to analyze their virus-neutralizing activity and to confirm absence of the antibody-mediated enhancement of infection by the anti-RBD antibodies.
antibodies , antiviral properties , coronavirus infection , COVID-19 , RBD , receptor-binding domain , SARS-CoV-2
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Federal State Public Scientific Institution “Institute of Chemical Biology and Fundamental Medicine”, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
State Research Center of Virology and Biotechnology “VECTOR”, Federal Service for the Oversight of Consumer Protection and Welfare, Novosibirsk Region, Koltsovo, 630559, Russian Federation
FIC FTM, Novosibirsk, 630117, Russian Federation
Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies FMBA of Russia, Moscow, 115682, Russian Federation
Federal Center of Brain Research and Neurotechnologies, FMBA of Russia, Moscow, 117513, Russian Federation
Astana Medical University, Nur-Sultan, 010000, Kazakhstan
Pulmonology Research Institute FMBA of Russia, Moscow, 115682, Russian Federation
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russian Federation
Novosibirsk State University, Novosibirsk, 630090, Russian Federation
Federal State Public Scientific Institution “Institute of Chemical Biology and Fundamental Medicine”
State Research Center of Virology and Biotechnology “VECTOR”
FIC FTM
Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies FMBA of Russia
Federal Center of Brain Research and Neurotechnologies
Astana Medical University
Pulmonology Research Institute FMBA of Russia
Engelhardt Institute of Molecular Biology
Novosibirsk State University
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