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...

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Main Authors: I. K. Baykov, A. L. Matveev, L. A. Emelianova, G. B. Kaverina, S. E. Tkachev, N. V. Tikunova
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2019-05-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/2016
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author I. K. Baykov
A. L. Matveev
L. A. Emelianova
G. B. Kaverina
S. E. Tkachev
N. V. Tikunova
author_facet I. K. Baykov
A. L. Matveev
L. A. Emelianova
G. B. Kaverina
S. E. Tkachev
N. V. Tikunova
author_sort I. K. Baykov
collection DOAJ
description 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.
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institution Kabale University
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publishDate 2019-05-01
publisher Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
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series Вавиловский журнал генетики и селекции
spelling doaj-art-ae03e8ff830048939c1bd3d9622c5ac12025-02-01T09:58:07ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592019-05-0123325626110.18699/VJ19.490902The 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 antibodyI. K. Baykov0A. L. Matveev1L. A. Emelianova2G. B. Kaverina3S. E. Tkachev4N. V. Tikunova5Institute of Сhemical Biology аnd Fundamental Medicine, SB RASInstitute of Сhemical Biology аnd Fundamental Medicine, SB RAS; Novosibirsk State UniversityInstitute of Сhemical Biology аnd Fundamental Medicine, SB RAS; Novosibirsk State UniversityInstitute of Сhemical Biology аnd Fundamental Medicine, SB RASInstitute of Сhemical Biology аnd Fundamental Medicine, SB RASInstitute of Сhemical Biology аnd Fundamental Medicine, SB RAS; Novosibirsk State UniversityCurrently, 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.https://vavilov.elpub.ru/jour/article/view/2016tick-borne encephalitis virusglycoprotein edomain d3antibodyrecombinant proteinsurface plasmon resonanceepitope mapping
spellingShingle I. K. Baykov
A. L. Matveev
L. A. Emelianova
G. B. Kaverina
S. E. Tkachev
N. V. Tikunova
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
Вавиловский журнал генетики и селекции
tick-borne encephalitis virus
glycoprotein e
domain d3
antibody
recombinant protein
surface plasmon resonance
epitope mapping
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic tick-borne encephalitis virus
glycoprotein e
domain d3
antibody
recombinant protein
surface plasmon resonance
epitope mapping
url https://vavilov.elpub.ru/jour/article/view/2016
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