TY - JOUR

T1 - Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19

AU - Matveev, Andrey

AU - Pyankov, Oleg

AU - Khlusevich, Yana

AU - Tyazhelkova, Olga

AU - Emelyanova, Lyudmila

AU - Timofeeva, Anna

AU - Shipovalov, Andrey

AU - Chechushkov, Anton

AU - Zaitseva, Natalia

AU - Kudrov, Gleb

AU - Yusubalieva, Gaukhar

AU - Yussubaliyeva, Saule

AU - Zhukova, Oxana

AU - Baklaushev, Vladimir

AU - Sedykh, Sergey

AU - Lifshits, Galina

AU - Tikunov, Artem

AU - Tikunova, Nina

N1 - Funding: This research was funded by the Russian Science Foundation, Project No. 21-74-00141. CHO-S cells and expression plasmid pOptiCAG were obtained from the Collection of Extremophile Microorganisms and Type Cultures of ICBFM SB RAS, which is supported by the Ministry of Education and Science, Project No. 121031300043-8.

PY - 2023/6/28

Y1 - 2023/6/28

N2 - 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 IC50 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.

AB - 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 IC50 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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85164843759&origin=inward&txGid=8c58ee2913d70ee79265e0e07f235cda

UR - https://www.mendeley.com/catalogue/9ba2462c-2a22-389d-9b49-5b1915587686/

U2 - 10.3390/ijms241310799

DO - 10.3390/ijms241310799

M3 - Article

C2 - 37445984

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 13

M1 - 10799

ER -