The effect of differences in the third domain of the glycoprotein E of tick-borne encephalitis virus of the Far Eastern, Siberian and European subtypes on the binding of recombinant D3 proteins with a chimeric antibody

Currently, a therapeutic drug based on recombinant antibodies for the prevention and treatment of tick-borne encephalitis virus (TBEV) is developed in ICBFM SB RAS, and the chimeric antibody ch14D5 is considered as one of the key components of this drug. It was previously shown that this antibody is directed to the domain D3 of the glycoprotein E of TBEV. It was previously shown that this antibody is able to protect mice from the European subtype of TBEV, strain “Absettarov”, and the presence of virus-neutralizing activity against the Far Eastern subtype of TBEV, strain 205 was also shown for this antibody. However, it remains unclear whether this antibody exhibits selectivity for different subtypes of TBEV. The aim of this study was to investigate the effect of amino acid sequence differences of recombinant D3 domains derived from the glycoprotein E of TBEV of the Far Eastern, Siberian and European subtypes on the binding of the protective antibody ch14D5 to these proteins. Using Western blot analysis and surface plasmon resonance, it was shown that ch14D5 antibody has the highest affinity (KD= 1.7±0.5 nM) for the D3 domain of the TBEV of the “Sofjin-Ru” strain belonging to the Far Eastern subtype of the virus. At the same time, the affinity of ch14D5 antibody for similar D3 proteins derived from “Zausaev”, “1528-99” and “Absettarov” strains of the Siberian and European subtypes of TBEV was noticeably lower (KD= 25±4, 300±50, 250±50 nM, respectively). In addition, information about the spatial arrangement of amino acid residues that are different for the studied recombinant proteins indicates that the epitope recognized by the ch14D5 antibody is in close proximity to the lateral ridge of D3 domain of E glycoprotein

Контролируемые исследования по эффективности поликомпонентной вакцины при иммунотерапии у больных с хроническими обструктивными заболеваниями органов дыхания

During the hard controlled study, the effeciency of polycomponent vaccina designed by SRI of I.I.Mechnikov was investigated. The satisfactory and excelent effect was found in 71.4% of patients, that expressed in the listening of remission, the decrease of the exacerbation frequency and the severity of the disease course, the decrease of the quantity of medication, the improvement of respiration. Vaccina therapy induces the increase of the level of antibodies to all the antigen components of the vaccina in the patients. The number of patients with low titres of the antibodies decreases and the number of patients with high ones increases. Vaccina therapy with VP-4 used in according to the offered medication scheme does not induce the increase of the total IgE level in serum. There is the sharp decrease of this parameter in patients with the initial high level of IgE.В строго контролируемом опыте изучена эффективность поликомпонентной вакцины НИИ ВС им. И.И. Мечникова. Установлен хороший и отличный терапевтический эффект у 71,4% больных, что выражается в удлинении сроков ремиссии у больных, снижении частоты обострений и тяжести течения заболевания, сокращении количества принимаемых лекарств, улучшении показателей функции внешнего дыхания. Вакцинотерапия вызывает у больных подъем уровня антител ко всем антигенным компонентам вакцины. Уменьшается число больных с низкими титрами и увеличивается количество больных с высокими титрами антител. Вакцинотерапия ВП-4 по предложенной схеме введения не вызывает подъем уровня общего иммуноглобулина Е в сыворотке крови больных. У больных с исходно высоким уровнем иммуноглобулина Е отмечается выраженное снижение этого показателя

Lasp-1 Regulates Podosome Function

Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins