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

• Published in: International journal of molecular sciences 2018-09, Vol.19 (10), p.2988
• Main Authors: Sanina, Nina, Chopenko, Natalia, Mazeika, Andrey, Davydova, Ludmila, Leonova, Galina, Stenkova, Anna, Uversky, Vladimir N, Kostetsky, Eduard
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - blood; Antigens - immunology; Encephalitis Viruses, Tick-Borne - metabolism; Galactolipids - metabolism; Immunization; Mice, Inbred BALB C; Porins - chemistry; Protein Domains; Recombinant Fusion Proteins - immunology; Viral Envelope Proteins - chemistry; Yersinia pseudotuberculosis - metabolism
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms19102988

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 (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.