Antibodies Capable of Enhancing SARS-CoV-2 Infection Can Circulate in Patients with Severe COVID-19
Matveev A. Pyankov O. Khlusevich Y. Tyazhelkova O. Emelyanova L. Timofeeva A. Shipovalov A. Chechushkov A. Zaitseva N. Kudrov G. Yusubalieva G. Yussubaliyeva S. Zhukova O. Baklaushev V. Sedykh S. Lifshits G. Tikunov A. Tikunova N.
July 2023Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2023#24Issue 13
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.
ADE , antibody-dependent enhancement , COVID-19 , monoclonal antibody , SARS-CoV-2 , virus neutralizing antibody
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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”, Rospotrebnadzor, Koltsovo, 630559, Russian Federation
Laboratory of Molecular Epidemiology and Biodiversity of Viruses, Research Institute of Virology, Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, 630117, Russian Federation
Federal Research and Clinical Center for Specialized Types of 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
Department of General Medical Practice with the Course of Evidence-Based Medicine, 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
Faculty of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russian Federation
Institute of Chemical Biology and Fundamental Medicine
State Research Center of Virology and Biotechnology “VECTOR”
Laboratory of Molecular Epidemiology and Biodiversity of Viruses
Federal Research and Clinical Center for Specialized Types of Medical Care and Medical Technologies FMBA of Russia
Federal Center of Brain Research and Neurotechnologies
Department of General Medical Practice with the Course of Evidence-Based Medicine
Pulmonology Research Institute
Engelhardt Institute of Molecular Biology
Faculty of Natural Sciences
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