Mechanisms of Protective Actions of Specific Antibodies against the Tick-Borne Encephalitis Virus

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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 5, September, 2020 IMMUNOLOGY AND MICROBIOLOGY

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Mechanisms of Protective Actions of Specific Antibodies against the Tick-Borne Encephalitis Virus G. N. Leonova

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 5, pp. 587-591, May, 2020 Original article submitted January 21, 2020 The protective mechanisms of specific antibodies against tick-borne encephalitis virus were demonstrated on in vitro model. The effect of specific IgG on tick-borne encephalitis virus was comprehensively assessed in virucidal, preventive, direct antiviral, and intracellular actions by ELISA and virus titration results. The IC50 values were obtained for virucidal (3.8±0.7 U/ml), preventive (42.8±9.9 U/ml), direct antiviral (7.2±0.9 U/ml), and intracellular action (1.7±0.4 U/ml). During titration of the samples, complete elimination of the virus was observed at IgG concentration of 16 U/ml (virucidal), 320 U/ml (preventive), 32 U/ml (direct antiviral), and 8 U/ml (intracellular action). It was demonstrated that specific IgG produces a complex inhibitory effect on tick-borne encephalitis virus: it possesses both direct neutralizing activity on the virus and reduces its adsorption and intracellular replication. Key Words: tick-borne encephalitis virus (TBEV); specific immunoglobulin; mechanisms of virus inhibition Tick-borne encephalitis (TBE), a neuroviral infection transmitted through the bites of ixodid ticks, is prevalent in natural foci of the Eurasian continent. To date, specific prevention remains the most effective way to combat this infection. Emergency prophylaxis with specific Ig is used after detection of an antigen or genetic marker of TBE virus (TBEV) in a sucking tick. Specific prophylaxis and treatment of TBE with immunoglobulin is widely used in Russia, due to the absence of effective drugs capable of inhibiting and eliminating the pathogen. At the same time, special preclinical and clinical studies in accordance with modern requirements for the drug “Human immunoglobulin against tick-borne encephalitis” have not yet been carried out [8]. The conflicting opinions of experts [1-3,6,7,] about its effectiveness dictate the need for such studies. Our aim was to demonstrate the protective mechanisms of specific antibodies against tick-borne encephalitis virus on an in vitro model. G. P. Somov Research Institute of Epidemiology and Microbiology, Vladivostok, Russia. Address for correspondence: galinaleon41@ gmail.com. G. N. Leonova

MATERIALS AND METHODS The study was performed on a SPEV porcine embryo kidney cell line. The cells were cultured in medium 199 (PanEco) with 10% fetal calf serum (HyClone). For the experiments, SPEV cells were seeded on 96well microplates and incubated at 37°C and 5% CO2. We also used TBEV strain Dal’negorsk isolated from the brain of a patient died from TBE. According to the results of its biological properties [11], this strain was characterized as high-virulent, and according to genome-wide sequencing, it