scholarly journals Computational and Rational Design of Single-Chain Antibody against Tick-Borne Encephalitis Virus for Modifying Its Specificity

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1494
Author(s):  
Ivan K. Baykov ◽  
Pavel Y. Desyukevich ◽  
Ekaterina E. Mikhaylova ◽  
Olga M. Kurchenko ◽  
Nina V. Tikunova
Keyword(s):  
Rational Design ◽  
Fold Increase ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Glycoprotein E ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

Tick-borne encephalitis virus (TBEV) causes 5−7 thousand cases of human meningitis and encephalitis annually. The neutralizing and protective antibody ch14D5 is a potential therapeutic agent. This antibody exhibits a high affinity for binding with the D3 domain of the glycoprotein E of the Far Eastern subtype of the virus, but a lower affinity for the D3 domains of the Siberian and European subtypes. In this study, a 2.2-fold increase in the affinity of single-chain antibody sc14D5 to D3 proteins of the Siberian and European subtypes of the virus was achieved using rational design and computational modeling. This improvement can be further enhanced in the case of the bivalent binding of the full-length chimeric antibody containing the identified mutation.

scholarly journals 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

2019 ◽  
Vol 23 (3) ◽  
pp. 256-261
Author(s):  
I. K. Baykov ◽  
A. L. Matveev ◽  
L. A. Emelianova ◽  
G. B. Kaverina ◽  
S. E. Tkachev ◽  
...  
Keyword(s):  
Amino Acid ◽  
Spatial Arrangement ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Therapeutic Drug ◽  
Glycoprotein E ◽  
Tick Borne Encephalitis ◽  
Tbev Strain ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

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.

scholarly journals Chimeric Antibody 14D5 Protects Mice against the Far-Eastern, Siberian, and European Tick-borne Encephalitis Virus

2019 ◽  
Vol 4 (1) ◽  
pp. 143-149
Author(s):  
Andrey L. Matveev ◽  
Irina V. Kozlova ◽  
Elena K. Doroshchenko ◽  
Oleg V. Stronin ◽  
Oksana V. Lisak ◽  
...  
Keyword(s):  
Protective Efficacy ◽  
Encephalitis Virus ◽  
Serum Immunoglobulin ◽  
Chimeric Antibody ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Exposure Prophylaxis ◽  
Far Eastern

Tick-borne encephalitis virus (TBEV), belonging to the Flaviviridae family, is the most significant pathogen transmitted by Ixodes ticks and causing one of the most severe human neuroinfections. In Russia, serum immunoglobulin produced from the donor blood is currently used for post-exposure prophylactic and therapy of tick-borne encephalitis virus. However, it is known that preparations obtained from donated blood have certain disadvantages, and therefore development of novel preparations for post exposure prophylaxis and therapy of tick-borne encephalitis is required. To develop an alternative preparation, which does not include donor blood, a chimeric antibody ch14D5 against glycoprotein E of TBEV was constructed.This study was aimed to investigate protective efficacy of the chimeric antibody ch14D5 against the Far-Eastern, Siberian, and European subtypes of TBEV in in vivo experiments.A peripheral mouse model of tick-borne encephalitis was used in this study: the chimeric antibody ch14D5 was administrated intravenously in mice one day after their intraperitoneal infection with TBEV strains Sofjin, Vasilchenko, and Absettarov. Anti-TBEV serum immunoglobulin was used as a control preparation, which was administered in the same way. Protective efficacy of the chimeric antibodies 14D5 was assessed using the log-rank test. In the study, the presence or absence of antibody-dependent enhancement of infection (ADE) was examined when mice, infected with different subtypes of the TBEV, got the antibody ch14d5.Obtained results demonstrated high efficacy of the ch14D5 antibody in post-exposure prophylaxis of the disease in mice infected with any of the used TBEV strains, as well as the absence of ADE.It was shown that protective efficacy of antibody ch14D5 is higher than that of the anti-TBEV serum immunoglobulin, and antibody ch14D5 could be used for development of a therapeutic preparation for post-exposure prophylaxis.

scholarly journals Structural insights into tick-borne encephalitis virus neutralization and animal protection by a therapeutic antibody

2021 ◽  
Author(s):  
Ivan K. Baykov ◽  
Grzegorz Chojnowski ◽  
Petr Pachl ◽  
Andrey L. Matveev ◽  
Nina A. Moor ◽  
...  
Keyword(s):  
Rational Design ◽  
Encephalitis Virus ◽  
Glycoprotein E ◽  
Animal Protection ◽  
X Ray Crystallography ◽  
Tick Borne Encephalitis ◽  
Late Endosomes ◽  
Lateral Ridge ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitis virus (TBEV) causes about 5-6 thousand cases annually, while there is still no effective treatment for this virus. To fill this gap, a high-affinity chimeric anti-TBEV antibody ch14D5 has previously been constructed, and high protective activity in a murine TBEV model has been shown for this antibody. However, the mechanism of action of this antibody and the recognized epitope have not been known yet. In this study, it is shown by X-ray crystallography that this antibody recognizes a unique epitope on the lateral ridge of the D3 domain of glycoprotein E, which is readily accessible for binding. The orientation of this antibody relative to the virion surface makes bivalent binding possible, which facilitates the cross-linking of glycoprotein E molecules and thus blocking of surface rearrangements required for infection. Since the antibody tightly binds to this protein even at pH ~ 5.0, it locks the virion in an acidic environment inside the late endosomes or phagosomes and, therefore, effectively blocks the fusion of the viral and endosomal/phagosomal membranes. We believe that this is why the ch14D5 antibody does not induce an antibody-dependent enhancement of infection in vivo, which is critical in the development of antibody-based therapeutic agents. In addition, the structure of the antibody-glycoprotein E interface can be used for the rational design of this antibody for enhancing its properties.

scholarly journals Post-exposure administration of chimeric antibody protects mice against European, Siberian, and Far-Eastern subtypes of tick-borne encephalitis virus

PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215075 ◽  
Author(s):  
Andrey L. Matveev ◽  
Irina V. Kozlova ◽  
Oleg V. Stronin ◽  
Yana A. Khlusevich ◽  
Elena K. Doroshchenko ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Post Exposure ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

scholarly journals ANALYSIS OF DOMAIN SPECIFICITY OF THE PROTECTIVE CHIMERIC ANTIBODY ch14D5a AGAINST GLYCOPROTEIN E OF TICK-BORNE ENCEPHALITIS VIRUS

2018 ◽  
Vol 22 (4) ◽  
pp. 459-467 ◽  
Author(s):  
I. K. Baykov ◽  
L. A. Emelyanova ◽  
L. M. Sokolova ◽  
E. M. Karelina ◽  
A. L. Matveev ◽  
...  
Keyword(s):  
Expression System ◽  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Fab Fragment ◽  
Surface Plasmon Resonance Analysis ◽  
Glycoprotein E ◽  
Resonance Analysis ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
System 1

A drug for the prevention and therapy of tick-borne encephalitis virus is being developed on the basis of the protective chimeric antibody ch14D5a. At the same time, the epitope recognized by this antibody on the surface of glycoprotein E has not been localized yet. The aim of this work was to identify the domain of glycoprotein E, to which the protective antibody ch14D5a binds. As a result, four recombinant variants of glycoprotein E were generated using the bacterial expression system: (1) the rE protein containing the domains D1, D2, and D3 of glycoprotein E; (2) the rED1+2 protein containing domains D1 and D2; (3) the rED3_301 protein, which is domain D3 of glycoprotein E, and (4) the rED3_294 protein comprising domain D3 and a hinge region connecting domains D1 and D3. The rED3_294 and rED3_301 proteins were obtained in soluble monomeric form. The rE and rED1+2 proteins were extracted from the inclusion bodies of Escherichia coli. Using Western blot analysis and surface plasmon resonance analysis, it was demonstrated that the protective chimeric antibody ch14D5a and its Fab fragment bound specifically to domain D3 of glycoprotein E. Since the antibodies recognizing epitopes on the surface of domain D3 do not tend to cause antibody-dependent enhancement of the infection as compared to antibodies directed to domains D1 and D2, the data obtained confirm the promise of using the antibody ch14D5a in the development of a therapeutic preparation against the tick-borne encephalitis virus.

A protective chimeric antibody to tick-borne encephalitis virus

Vaccine ◽  
2014 ◽  
Vol 32 (29) ◽  
pp. 3589-3594 ◽  
Author(s):  
Ivan K. Baykov ◽  
Andrey L. Matveev ◽  
Oleg V. Stronin ◽  
Alexander B. Ryzhikov ◽  
Leonid E. Matveev ◽  
...  
Keyword(s):  
Encephalitis Virus ◽  
Chimeric Antibody ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Tick-borne encephalitides

2011 ◽  
Author(s):  
Patricia A. Nuttall
Keyword(s):  
North America ◽  
Tick Species ◽  
Encephalitis Virus ◽  
Virus Family ◽  
Wild Mammals ◽  
Tick Borne Encephalitis ◽  
Powassan Virus ◽  
Louping Ill ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern

Tick-borne encephalitides are caused by three different viruses transmitted by ticks and belonging to the Flaviviridae virus family: tick-borne encephalitis virus (Far Eastern, Siberian, and European subtypes), louping ill virus, and Powassan virus (including deer tick virus). These viruses cause encephalitis affecting humans in Eurasia and North America. In nature, they are maintained in transmission cycles involving Ixodes tick species and small or medium-sized wild mammals. The tick-borne flavivirus group is one of the most intensely studied groups of tick-borne pathogens.

Evaluation of European tick-borne encephalitis virus vaccine against recent Siberian and far-eastern subtype strains

Vaccine ◽  
2001 ◽  
Vol 19 (32) ◽  
pp. 4774-4779 ◽  
Author(s):  
Daisuke Hayasaka ◽  
Akiko Goto ◽  
Kentarou Yoshii ◽  
Tetsuya Mizutani ◽  
Hiroaki Kariwa ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Encephalitis Virus ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Far Eastern
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