Cargando…

Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex

Tick-borne encephalitis (TBE) is a widespread, dangerous infection. Unfortunately, all attempts to create safe anti-TBE subunit vaccines are still unsuccessful due to their low immunogenicity. The goal of the present work was to investigate the immunogenicity of a recombinant chimeric protein create...

Descripción completa

Detalles Bibliográficos
Autores principales: Sanina, Nina, Chopenko, Natalia, Mazeika, Andrey, Davydova, Ludmila, Leonova, Galina, Stenkova, Anna, Uversky, Vladimir N., Kostetsky, Eduard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213927/
https://www.ncbi.nlm.nih.gov/pubmed/30274357
http://dx.doi.org/10.3390/ijms19102988
_version_ 1783367889837883392
author Sanina, Nina
Chopenko, Natalia
Mazeika, Andrey
Davydova, Ludmila
Leonova, Galina
Stenkova, Anna
Uversky, Vladimir N.
Kostetsky, Eduard
author_facet Sanina, Nina
Chopenko, Natalia
Mazeika, Andrey
Davydova, Ludmila
Leonova, Galina
Stenkova, Anna
Uversky, Vladimir N.
Kostetsky, Eduard
author_sort Sanina, Nina
collection PubMed
description Tick-borne encephalitis (TBE) is a widespread, dangerous infection. Unfortunately, all attempts to create safe anti-TBE subunit vaccines are still unsuccessful due to their low immunogenicity. The goal of the present work was to investigate the immunogenicity of a recombinant chimeric protein created by the fusion of the EIII protein, comprising domain III and a stem region of the tick-borne encephalitis virus (TBEV) E protein, and the OmpF porin of Yersinia pseudotuberculosis (OmpF-EIII). Adjuvanted antigen delivery systems, the tubular immunostimulating complexes (TI-complexes) based on the monogalactosyldiacylglycerol from different marine macrophytes, were used to enhance the immunogenicity of OmpF-EIII. Also, the chimeric protein incorporated into the most effective TI-complex was used to study its protective activity. The content of anti-OmpF-EIII antibodies was estimated in mice blood serum by enzyme-linked immunosorbent assay (ELISA). To study protective activity, previously immunized mice were infected with TBEV strain Dal’negorsk (GenBank ID: FJ402886). The animal survival was monitored daily for 21 days. OmpF-EIII incorporated into the TI-complexes induced about a 30–60- and 5–10-fold increase in the production of anti-OmpF-EIII and anti-EIII antibodies, respectively, in comparison with the effect of an individual OmpF-EIII. The most effective vaccine construction provided 60% protection. Despite the dramatic effect on the specific antibody titer, the studied TI-complex did not provide a statistically significant increase in the protection of OmpF-EIII protein. However, our results provide the basis of the future search for approaches to design and optimize the anti-TBEV vaccine based on the OmpF-EIII protein.
format Online
Article
Text
id pubmed-6213927
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62139272018-11-14 Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex Sanina, Nina Chopenko, Natalia Mazeika, Andrey Davydova, Ludmila Leonova, Galina Stenkova, Anna Uversky, Vladimir N. Kostetsky, Eduard Int J Mol Sci Article Tick-borne encephalitis (TBE) is a widespread, dangerous infection. Unfortunately, all attempts to create safe anti-TBE subunit vaccines are still unsuccessful due to their low immunogenicity. The goal of the present work was to investigate the immunogenicity of a recombinant chimeric protein created by the fusion of the EIII protein, comprising domain III and a stem region of the tick-borne encephalitis virus (TBEV) E protein, and the OmpF porin of Yersinia pseudotuberculosis (OmpF-EIII). Adjuvanted antigen delivery systems, the tubular immunostimulating complexes (TI-complexes) based on the monogalactosyldiacylglycerol from different marine macrophytes, were used to enhance the immunogenicity of OmpF-EIII. Also, the chimeric protein incorporated into the most effective TI-complex was used to study its protective activity. The content of anti-OmpF-EIII antibodies was estimated in mice blood serum by enzyme-linked immunosorbent assay (ELISA). To study protective activity, previously immunized mice were infected with TBEV strain Dal’negorsk (GenBank ID: FJ402886). The animal survival was monitored daily for 21 days. OmpF-EIII incorporated into the TI-complexes induced about a 30–60- and 5–10-fold increase in the production of anti-OmpF-EIII and anti-EIII antibodies, respectively, in comparison with the effect of an individual OmpF-EIII. The most effective vaccine construction provided 60% protection. Despite the dramatic effect on the specific antibody titer, the studied TI-complex did not provide a statistically significant increase in the protection of OmpF-EIII protein. However, our results provide the basis of the future search for approaches to design and optimize the anti-TBEV vaccine based on the OmpF-EIII protein. MDPI 2018-09-30 /pmc/articles/PMC6213927/ /pubmed/30274357 http://dx.doi.org/10.3390/ijms19102988 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sanina, Nina
Chopenko, Natalia
Mazeika, Andrey
Davydova, Ludmila
Leonova, Galina
Stenkova, Anna
Uversky, Vladimir N.
Kostetsky, Eduard
Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title_full Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title_fullStr Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title_full_unstemmed Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title_short Immunogenicity and Protective Activity of a Chimeric Protein Based on the Domain III of the Tick-Borne Encephalitis Virus E Protein and the OmpF Porin of Yersinia pseudotuberculosis Incorporated into the TI-Complex
title_sort immunogenicity and protective activity of a chimeric protein based on the domain iii of the tick-borne encephalitis virus e protein and the ompf porin of yersinia pseudotuberculosis incorporated into the ti-complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213927/
https://www.ncbi.nlm.nih.gov/pubmed/30274357
http://dx.doi.org/10.3390/ijms19102988
work_keys_str_mv AT saninanina immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT chopenkonatalia immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT mazeikaandrey immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT davydovaludmila immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT leonovagalina immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT stenkovaanna immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT uverskyvladimirn immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex
AT kostetskyeduard immunogenicityandprotectiveactivityofachimericproteinbasedonthedomainiiiofthetickborneencephalitisviruseproteinandtheompfporinofyersiniapseudotuberculosisincorporatedintotheticomplex