Abstract

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

Andrey L. Matveev^1,a*, Oleg V. Pyankov², Yana A. Khlusevich¹, Olga V. Tyazhelkova¹, Ljudmila A. Emelyanova¹, Anna M. Timofeeva¹, Andrey V. Shipovalov², Anton V. Chechushkov¹, Natalia S. Zaitseva³, Gleb A. Kudrov², Gaukhar M. Yusubalieva^4,5, Saule M. Yussubaliyeva⁶, Oxana A. Zhukova⁴, Artem Yu. Tikunov¹, Vladimir P. Baklaushev^4,7,8, Sergey E. Sedykh⁹, Galina I. Lifshits¹, and Nina V. Tikunova^1,9

¹Federal State Public Scientific Institution “Institute of Chemical Biology and Fundamental Medicine”, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia

²State Research Center of Virology and Biotechnology “VECTOR”, Federal Service for the Oversight of Consumer Protection and Welfare, 630559 Koltsovo, Novosibirsk Region, Russia

³FIC FTM, 630117 Novosibirsk, Russia

⁴Federal Research and Clinical Center of Specialized Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, Russia

⁵Federal Center of Brain Research and Neurotechnologies, FMBA of Russia, 117513 Moscow, Russia

⁶Astana Medical University, 010000 Nur-Sultan, Kazakhstan

⁷Pulmonology Research Institute FMBA of Russia, 115682 Moscow, Russia

⁸Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

⁹Novosibirsk State University, 630090 Novosibirsk, Russia

^* To whom correspondence should be addressed.

Received April 25, 2023; Revised August 14, 2023; Accepted August 18, 2023
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.
KEY WORDS: coronavirus infection, SARS-CoV-2, COVID-19, RBD, antibodies, receptor-binding domain, antiviral properties
DOI: 10.1134/S000629792309002X