TY - JOUR

T1 - 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

AU - Matveev, Andrey L

AU - Pyankov, Oleg V

AU - Khlusevich, Yana A

AU - Tyazhelkova, Olga V

AU - Emelyanova, Ljudmila A

AU - Timofeeva, Anna M

AU - Shipovalov, Andrey V

AU - Chechushkov, Anton V

AU - Zaitseva, Natalia S

AU - Kudrov, Gleb A

AU - Yusubalieva, Gaukhar M

AU - Yussubaliyeva, Saule M

AU - Zhukova, Oxana A

AU - Tikunov, Artem Yu

AU - Baklaushev, Vladimir P

AU - Sedykh, Sergey E

AU - Lifshits, Galina I

AU - Tikunova, Nina V

N1 - This work was supported by the Russian Science Foundation (grant no. 21-74-00141). Expression plasmids pT4-HB-pCAG, CHO-S and SP 2/0 cells were obtained from the Collection of Extremophilic Microorganisms and Type Cultures of ICBFM SB RAS, which is supported by the Ministry of Science and Higher Education of the Russian Federation, project no. 121031300043-8.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - Animals

KW - Mice

KW - Humans

KW - COVID-19

KW - SARS-CoV-2/metabolism

KW - Antibodies, Neutralizing/chemistry

KW - Epitopes, B-Lymphocyte

KW - Antibodies, Viral

KW - coronavirus infection

KW - antiviral properties

KW - receptor-binding domain

KW - SARS-CoV-2

KW - RBD

KW - antibodies

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85171851875&origin=inward&txGid=3943b4159d068f8e779340baaee6c151

UR - https://www.mendeley.com/catalogue/ec5c6f5d-b0d4-366d-ab31-f33415c937ae/

U2 - 10.1134/S000629792309002X

DO - 10.1134/S000629792309002X

M3 - Article

C2 - 37770389

VL - 88

SP - 1205

EP - 1214

JO - Biochemistry (Moscow)

JF - Biochemistry (Moscow)

SN - 0006-2979

IS - 9

ER -