title: Recombinant domains III of Tick-Borne Encephalitis Virus envelope protein in combination with dextran and CpGs induce immune response and partial protectiveness against TBE virus infection in mice.
abstract: BACKGROUND
  E protein of tick-borne encephalitis virus (TBEV) and other flaviviruses is located on the surface of the viral particle. Domain III of this protein seems to be a promising component of subunit vaccines for prophylaxis of TBE and kits for diagnostics of TBEV.
  
  
  METHODS
  Three variants of recombinant TBEV E protein domain III of European, Siberian and Far Eastern subtypes fused with dextran-binding domain of Leuconostoc citreum KM20 were expressed in E. coli and purified. The native structure of domain III was confirmed by ELISA antibody kit and sera of patients with tick-borne encephalitis. Immunogenic and protective properties of the preparation comprising these recombinant proteins immobilized on a dextran carrier with CpG oligonucleotides as an adjuvant were investigated on the mice model.
  
  
  RESULTS
  All 3 variants of recombinant proteins immobilized on dextran demonstrate specific interaction with antibodies from the sera of TBE patients. Thus, constructed recombinant proteins seem to be promising for TBE diagnostics. The formulation comprising the 3 variants of recombinant antigens immobilized on dextran and CpG oligonucleotides, induces the production of neutralizing antibodies against TBEV of different subtypes and demonstrates partial protectivity against TBEV infection.
  
  
  CONCLUSIONS
  Studied proteins interact with the sera of TBE patients, and, in combination with dextran and CPGs, demonstrate immunogenicity and limited protectivity on mice compared with reference "Tick-E-Vac" vaccine.
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia. asershova@gmail.com.|Institute of Agricultural Biotechnology, Moscow, 127550, Russia. asershova@gmail.com.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia. asershova@gmail.com.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Ershova
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Gra
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lyaschuk
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Tatyana M
authors.initials: TM
authors.lastname: Grunina
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Artem P
authors.initials: AP
authors.lastname: Tkachuk
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Bartov
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Darya M
authors.initials: DM
authors.lastname: Savina
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.|Institute of Agricultural Biotechnology, Moscow, 127550, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Sergienko
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Zoya M
authors.initials: ZM
authors.lastname: Galushkina
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Gudov
authors.affiliation: Chumakov Institute of poliomyelitis and viral encephalitides, Moscow, 142782, Russia.
authors.forename: Liubov I
authors.initials: LI
authors.lastname: Kozlovskaya
authors.affiliation: Chumakov Institute of poliomyelitis and viral encephalitides, Moscow, 142782, Russia.
authors.forename: Ivan S
authors.initials: IS
authors.lastname: Kholodilov
authors.affiliation: Chumakov Institute of poliomyelitis and viral encephalitides, Moscow, 142782, Russia.
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Gmyl
authors.affiliation: Chumakov Institute of poliomyelitis and viral encephalitides, Moscow, 142782, Russia.
authors.forename: Galina G
authors.initials: GG
authors.lastname: Karganova
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.|Institute of Agricultural Biotechnology, Moscow, 127550, Russia.
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Lunin
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.|Institute of Agricultural Biotechnology, Moscow, 127550, Russia.|Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Karyagina
authors.affiliation: Gamaleya Center of Epidemiology and Microbiology, Moscow, 123098, Russia.
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gintsburg
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D018899:CpG Islands; D003911:Dextrans / Q000378:metabolism; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology* / Q000472:pathogenicity; D004675:Encephalitis, Tick-Borne / Q000276:immunology* / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D000072417:Protein Domains / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D003911:Dextrans; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C065696:glycoprotein E, Flavivirus
keywords: CpG oligonucleotides; Dextran-binding domain; Domain III; Envelope protein; Tick-borne encephalitis virus