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

Nina Sanina,Anna Stenkova,Galina Leonova,Ludmila Davydova,Andrey Mazeika,Natalia Chopenko,Eduard Kostetsky,Vladimir Uversky

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.

Highlights

Tick-borne encephalitis (TBE) is a widespread infection of the central nervous system, which is induced by the tick-borne encephalitis virus (TBEV) belonging to the genus Flavivirus of the Flaviviridae family
Recombinant strategies are dominant in the elaboration of modern subunit vaccines, primarily due to the safety and reproducibility of the procedures utilized for obtaining recombinant proteins in comparison with the procedures used in obtaining proteins directly from the pathogens
There is a clear need for development of new and improved adjuvants for the development of vaccines, in particular those that are based on the highly pure, but poorly immunogenic recombinant proteins

Summary

Introduction

Tick-borne encephalitis (TBE) is a widespread infection of the central nervous system, which is induced by the tick-borne encephalitis virus (TBEV) belonging to the genus Flavivirus of the Flaviviridae family. The development of new vaccines with a safe production process that could cause prolonged immunity without additional revaccinations is needed [3] In connection with this need, the current trend is the creation of safe subunit vaccines, which contain only the part of the pathogen (antigen) that is responsible for producing anti-infectious immunity in animals or humans. The use of purposefully constructed recombinant chimeric proteins with given properties is a new promising approach to the creation of subunit vaccines. Such antigens are generally poorly immunogenic, and need specific adjuvants [4]. A few of them are suitable for medical and veterinary vaccines in spite of a wide arsenal of available adjuvants [5,6]

Objectives

Methods

Results

Conclusion