{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:04:41Z","timestamp":1760241881065,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T00:00:00Z","timestamp":1538265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["15-15-00035-P"],"award-info":[{"award-number":["15-15-00035-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019negorsk (GenBank ID: FJ402886). The animal survival was monitored daily for 21 days. OmpF-EIII incorporated into the TI-complexes induced about a 30\u201360- and 5\u201310-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.<\/jats:p>","DOI":"10.3390\/ijms19102988","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T08:23:50Z","timestamp":1538468630000},"page":"2988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-691X","authenticated-orcid":false,"given":"Nina","family":"Sanina","sequence":"first","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-517X","authenticated-orcid":false,"given":"Natalia","family":"Chopenko","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Mazeika","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludmila","family":"Davydova","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Leonova","sequence":"additional","affiliation":[{"name":"Somov Institute of Epidemiology and Microbiology, 1 Selskaya st., Vladivostok 690087, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Stenkova","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"},{"name":"G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS, Prospect 100 let Vladivostoku, 159, Vladivostok 690022, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and USF Health Byrd Alzheimer\u2019s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33612, USA"},{"name":"Laboratory of New methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Pushchino 142290, Moscow Region, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Kostetsky","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University, 8 Sukhanova St., Vladivostok 690091, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0065-3527(03)61008-0","article-title":"Tick-borne flaviviruses","volume":"61","author":"Gritsun","year":"2003","journal-title":"Adv. Virus Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"430","DOI":"10.12998\/wjcc.v3.i5.430","article-title":"Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management","volume":"3","author":"Bogovic","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ershova, A.S., Gra, O.A., Lyaschuk, A.M., Grunina, T.M., Tkachuk, A.P., Bartov, M.S., Savina, D.M., Sergienko, O.V., Galushkina, Z.M., and Gudov, V.P. (2016). 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. BMC Infect. Dis., 16.","DOI":"10.1186\/s12879-016-1884-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1080\/21645515.2016.1229719","article-title":"Recent advancements in combination subunit vaccine development","volume":"13","author":"Tan","year":"2017","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sanina, N., Chopenko, N., Mazeika, A., and Kostetsky, E. (2017). Nanoparticulate tubular immunostimulating complexes: Novel formulation of effective adjuvants and antigen delivery systems. Biomed. Res. Int.","DOI":"10.1155\/2017\/4389525"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.4110\/in.2015.15.2.51","article-title":"Recent advances of vaccine adjuvants for infectious diseases","volume":"15","author":"Lee","year":"2015","journal-title":"Immune Netw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1586\/erv.12.86","article-title":"Vaccines and vaccination against tick-borne encephalitis","volume":"11","author":"Kollaritsch","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, X., Jia, R., Shen, H., Wang, M., Yin, Z., and Cheng, A. (2017). Structures and functions of the envelope glycoprotein in flavivirus infections. Viruses, 9.","DOI":"10.3390\/v9110338"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.biologicals.2010.07.004","article-title":"Domain III peptides from flavivirus envelope protein are useful antigens for serologic diagnosis and targets for immunization","volume":"38","author":"Silva","year":"2010","journal-title":"Biologicals"},{"key":"ref_10","first-page":"974","article-title":"Engineering of chimeric protein based on E protein domain III of tick-borne encephalitis virus and OmpF porin of Yersinia pseudotuberculosis","volume":"24","author":"Stenkova","year":"2017","journal-title":"Protein Pept. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1477-3155-9-35","article-title":"Tubular immunostimulating complex based on cucumarioside A2-2 and monogalactosyldiacylglycerol from marine macrophytes","volume":"9","author":"Kostetsky","year":"2011","journal-title":"J. Nanobiotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.phytochem.2004.01.013","article-title":"Fatty acid composition of individual polar lipid classes from marine macrophytes","volume":"65","author":"Sanina","year":"2004","journal-title":"Phytochemistry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.phytochem.2008.01.014","article-title":"Seasonal change of fatty acid composition and thermotropic behavior of polar lipids from marine macrophytes","volume":"69","author":"Sanina","year":"2008","journal-title":"Phytochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1016\/j.biochi.2012.01.009","article-title":"The influence of monogalactosyldiacylglycerols from different marine macrophytes on immunogenicity and conformation of protein antigen of tubular immunostimulating complex","volume":"94","author":"Sanina","year":"2012","journal-title":"Biochimie"},{"key":"ref_15","first-page":"202","article-title":"On the possibility of lipid-induced regulation of conformation and immunogenicity of influenza A Virus H1\/N1 hemagglutinin as antigen of TI-complexes","volume":"24","author":"Vorobieva","year":"2014","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sanina, N., Davydova, L., Chopenko, N., Kostetsky, E., and Shnyrov, V. (2017). Modulation of immunogenicity and conformation of HA1 subunit of influenza A virus H1\/N1 hemagglutinin in tubular immunostimulating complexes. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18091895"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.4049\/jimmunol.1300787","article-title":"Targeting uptake receptors on human plasmacytoid dendritic cells triggers antigen cross-presentation and robust type I IFN secretion","volume":"191","author":"Tel","year":"2013","journal-title":"J. Immunol."},{"key":"ref_18","first-page":"94","article-title":"Molecular pato-physiology of chronic virus infections","volume":"41","author":"Novitskiy","year":"2010","journal-title":"Usp. Fiziol. Nauk"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6756","DOI":"10.4049\/jimmunol.163.12.6756","article-title":"A DNA immunization model study with constructs expressing the tick-borne encephalitis virus envelope protein E in different physical forms","volume":"163","author":"Aberle","year":"1999","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1134\/S1063074015010101","article-title":"The effects of triterpene glycosides and phospholipids from marine invertebrates in the composition of tubular immunostimulating complexes on the immunogenicity of human serum albumin","volume":"41","author":"Vorobyeva","year":"2015","journal-title":"Russ. J. Mar. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.virol.2013.04.029","article-title":"Comprehensive assessment of the genetics and virulence of tick-borne encephalitis virus strains isolated from patients with inapparent and clinical forms of the infection in the Russian Far East","volume":"443","author":"Leonova","year":"2013","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Belikov, S.I., Kondratov, I.G., Potapova, U.V., and Leonova, G.N. (2014). The relationship between the structure of the tick-borne encephalitis virus strains and their pathogenic properties. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094946"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.bbapap.2010.01.011","article-title":"PONDR-FIT: A meta-predictor of intrinsically disordered amino acids","volume":"1804","author":"Xue","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/1097-0134(20010101)42:1<38::AID-PROT50>3.0.CO;2-3","article-title":"Sequence complexity of disordered protein","volume":"42","author":"Romero","year":"2001","journal-title":"Proteins"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/prot.20735","article-title":"Exploiting heterogeneous sequence properties improves prediction of protein disorder","volume":"61","author":"Obradovic","year":"2005","journal-title":"Proteins"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"i489","DOI":"10.1093\/bioinformatics\/btq373","article-title":"Improved sequence-based prediction of disordered regions with multilayer fusion of multiple information sources","volume":"26","author":"Mizianty","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1093\/bioinformatics\/bti541","article-title":"IUPred: Web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content","volume":"21","author":"Dosztanyi","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1142\/S0219720005000886","article-title":"Optimizing long intrinsic disorder predictors with protein evolutionary information","volume":"3","author":"Peng","year":"2005","journal-title":"J. Bioinform. Comput. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.2174\/138920312799277938","article-title":"Comprehensive comparative assessment of in-silico predictors of disordered regions","volume":"13","author":"Peng","year":"2012","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/07391102.2013.775969","article-title":"Accurate prediction of disorder in protein chains with a comprehensive and empirically designed consensus","volume":"32","author":"Fan","year":"2014","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S1093-3263(00)00138-8","article-title":"Intrinsically disordered protein","volume":"19","author":"Dunker","year":"2001","journal-title":"J. Mol. Graph. Model."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/prot.10532","article-title":"Predicting intrinsic disorder from amino acid sequence","volume":"53","author":"Obradovic","year":"2003","journal-title":"Proteins"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1093\/bioinformatics\/bti537","article-title":"FoldIndex: A simple tool to predict whether a given protein sequence is intrinsically unfolded","volume":"21","author":"Prilusky","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"956","DOI":"10.2174\/092986608785849164","article-title":"TOP-IDP-scale: A new amino acid scale measuring propensity for intrinsic disorder","volume":"15","author":"Campen","year":"2008","journal-title":"Protein Pept. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.jmb.2005.01.071","article-title":"The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins","volume":"347","author":"Dosztanyi","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/bioinformatics\/btu625","article-title":"Comprehensive large-scale assessment of intrinsic protein disorder","volume":"31","author":"Walsh","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_38","unstructured":"Peng, Z., and Kurgan, L. (2012). On the complementarity of the consensus-based disorder prediction. Pacific Symposium on Biocomputing. Pac. Symp. Biocomput., 176\u2013187."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/2988\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:23:21Z","timestamp":1760196201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/2988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,30]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19102988"],"URL":"https:\/\/doi.org\/10.3390\/ijms19102988","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,9,30]]}}}