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

Int J Mol Sci. 2018 Sep 30;19(10):2988. doi: 10.3390/ijms19102988.

Abstract

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.

Keywords: TBEV; fusion antigen; monogalactosyldiacylglycerol; nanoparticulate adjuvant; nanoparticulate delivery system; subunit vaccines.

MeSH terms

  • 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*

Substances

  • Antibodies
  • Antigens
  • Galactolipids
  • OmpF protein
  • Porins
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • monogalactosyldiacylglycerol
  • glycoprotein E, Flavivirus