Induction of humoral and cell-mediated immunity to the NS1 protein of TBEV with recombinant Influenza virus and MVA affords partial protection against lethal TBEV infection in mice

Front Immunol. 2023 Jul 7:14:1177324. doi: 10.3389/fimmu.2023.1177324. eCollection 2023.

Abstract

Introduction: Tick-borne encephalitis virus (TBEV) is one of the most relevant tick-transmitted neurotropic arboviruses in Europe and Asia and the causative agent of tick-borne encephalitis (TBE). Annually more than 10,000 TBE cases are reported despite having vaccines available. In Europe, the vaccines FSME-IMMUN® and Encepur® based on formaldehyde-inactivated whole viruses are licensed. However, demanding vaccination schedules contribute to sub-optimal vaccination uptake and breakthrough infections have been reported repeatedly. Due to its immunogenic properties as well as its role in viral replication and disease pathogenesis, the non-structural protein 1 (NS1) of flaviviruses has become of interest for non-virion based flavivirus vaccine candidates in recent years.

Methods: Therefore, immunogenicity and protective efficacy of TBEV NS1 expressed by neuraminidase (NA)-deficient Influenza A virus (IAV) or Modified Vaccinia virus Ankara (MVA) vectors were investigated in this study.

Results: With these recombinant viral vectors TBEV NS1-specific antibody and T cell responses were induced. Upon heterologous prime/boost regimens partial protection against lethal TBEV challenge infection was afforded in mice.

Discussion: This supports the inclusion of NS1 as a vaccine component in next generation TBEV vaccines.

Keywords: IAV; MVA; NS1; T cells; TBEV; protection; vaccination; virus-neutralizing antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • Encephalitis Viruses, Tick-Borne*
  • Encephalitis, Tick-Borne*
  • Humans
  • Immunity, Cellular
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Mice
  • Orthomyxoviridae*
  • Vaccinia virus

Substances

  • Antibodies, Viral
  • Influenza Vaccines

Supplementary concepts

  • Modified Vaccinia Ankara virus

Grants and funding

This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 398066876/GRK 2485/1 and the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the German Federal Ministry of Education and Research to GR. This Open Access publication was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491094227 “Open Access Publication Funding” and the University of Veterinary Medicine Hannover, Foundation. The funders played no role in study design, data collection, analysis and interpretation of data or the writing of this manuscript.