title: Evaluation of immune response and protective effect of four vaccines against the tick-borne encephalitis virus.
abstract: Among three main subtypes of the tick-borne encephalitis virus (TBEV), the Siberian subtype is currently dominant in a majority of the endemic regions of Russia. However, inactivated vaccines are based on TBEV strains of the heterologous Far Eastern or the European subtypes isolated 40-77 years ago. To analyze the efficacy of the available vaccines against currently prevailing TBEV isolates of the Siberian subtype, mice were immunized subcutaneously three times (one group per each vaccine). The expression of seven cytokine genes was determined using RT-PCR. Sera were studied using homologous and heterologous ELISA, hemagglutination inhibition (HI) and neutralization tests with TBEV strains of the Far Eastern, Siberian and European subtypes. Cross-protective efficacy of the vaccines was evaluated with the TBEV strain 2689 of Siberian subtype isolated from an ixodid tick from the Novosibirsk, South-Western Siberia, Russia in 2010. The cytokine gene expression profile indicates a predominantly Th2 response due to exogenous antigen presentation. Titers for homologous combinations of vaccine strain and strain in ELISA, HI and neutralization tests exceeded those for heterologous antigen-antibody pairs. Despite antibody detection by means of ELISA, HI and neutralization tests, the mouse protection afforded by the vaccines differed significantly. Complete protection of mice challenged with 100 LD50 virus of the Siberian subtype was induced by the vaccine "Encevir" ("Microgen", Tomsk, Russia). The minimal immunization doze (MID50) of "Encevir" protecting 50% of the mice was less than 0.0016 ml. Partial protective effect of vaccines produced in Moscow, Russia and Austria revealed MID50 within recommended intervals (0.001-0.017 ml). However, the MID50 for the vaccine "Encepur" (Novartis, Germany) 0.04 ml exceeded acceptable limits with total loss of mice immunized with vaccine diluted 32, 100 and 320 fold. These results suggest regular evaluation of TBEV vaccines in regions where heterologous virus subtypes prevail.
authors.affiliation: D.I. Ivanovsky Institute of Virology, 16 Gamaleya Street, 123098, Moscow, Russia; Research Institute for Physico-Chemical Medicine of the Federal Medical and Biological Agency of the Russian Federation, 1a Malaya Pirogovskaya Street, 119435 Moscow, Russia. Electronic address: omorozova2010@gmail.com.
authors.forename: O V
authors.initials: OV
authors.lastname: Morozova
authors.affiliation: Institute of Systematics and Ecology of Animals of the Siberian Branch of the Russian Academy of Sciences, 11 Frunze Street, 630091 Novosibirsk, Russia.
authors.forename: V N
authors.initials: VN
authors.lastname: Bakhvalova
authors.affiliation: Institute of Systematics and Ecology of Animals of the Siberian Branch of the Russian Academy of Sciences, 11 Frunze Street, 630091 Novosibirsk, Russia.
authors.forename: O F
authors.initials: OF
authors.lastname: Potapova
authors.affiliation: D.I. Ivanovsky Institute of Virology, 16 Gamaleya Street, 123098, Moscow, Russia.
authors.forename: A E
authors.initials: AE
authors.lastname: Grishechkin
authors.affiliation: D.I. Ivanovsky Institute of Virology, 16 Gamaleya Street, 123098, Moscow, Russia.
authors.forename: E I
authors.initials: EI
authors.lastname: Isaeva
authors.affiliation: Research Institute for Physico-Chemical Medicine of the Federal Medical and Biological Agency of the Russian Federation, 1a Malaya Pirogovskaya Street, 119435 Moscow, Russia.
authors.forename: K V
authors.initials: KV
authors.lastname: Aldarov
authors.affiliation: Research Institute for Physico-Chemical Medicine of the Federal Medical and Biological Agency of the Russian Federation, 1a Malaya Pirogovskaya Street, 119435 Moscow, Russia; M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
authors.forename: D V
authors.initials: DV
authors.lastname: Klinov
authors.affiliation: M.P. Chumakov Institute of Poliomyelitis and Viral Encephalites of the Russian Academy of Medical Sciences, 142782 Moscow, Russia.
authors.forename: M F
authors.initials: MF
authors.lastname: Vorovich
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D016207:Cytokines / Q000276:immunology; D004669:Encephalitis Viruses, Tick-Borne / Q000145:classification*; D004675:Encephalitis, Tick-Borne / Q000517:prevention & control*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; C464914:Encepur; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C065696:glycoprotein E, Flavivirus
keywords: Cytokines; ELISA; Hemagglutination inhibition; Inactivated vaccine; Neutralization test; Protective effect; Tick-borne flavivirus