Development of an mRNA Vaccine for Tick-Borne Encephalitis: Selection of a Prototype Virus Strain

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• Tick-borne encephalitis virus (TBEV) exhibits antigenic divergence among subtypes, complicating vaccine and antiviral development.
• Existing inactivated TBEV vaccines provide insufficient cross-protection against different strains.
• Breakthrough infections in vaccinated individuals highlight the need for broader TBEV immunity.

Purpose of the Study:

• To design and evaluate a novel mRNA vaccine candidate for tick-borne encephalitis virus (TBEV).
• To assess the immunogenicity and breadth of protective immunity elicited by candidate mRNA vaccines.
• To investigate the cross-protective efficacy against diverse TBEV strains.

Main Methods:

• Ten messenger RNA (mRNA) vaccine candidates encoding the TBEV Pre-Membrane/Envelope (PrM/E) proteins encapsulated in lipid nanoparticles (LNPs) were synthesized.
• Immunogenicity was assessed by measuring antigen-specific IgG and neutralizing antibody titers against multiple TBEV strains in BALB/c mice.
• Protective efficacy was evaluated through a lethal challenge model using seven distinct TBEV strains.

Main Results:

• All tested mRNA-PrM/E-LNP vaccine candidates achieved 100% survival in mice challenged with lethal doses of seven TBEV strains.
• The mRNA-PrM/E-Krasny Yar-8 construct exhibited superior immunogenicity, with a high antigen-specific IgG GMT of 1:6625.
• This leading candidate demonstrated the broadest in vitro virus-neutralizing activity against homologous and heterologous TBEV strains.

Conclusions:

• The mRNA vaccine platform is a highly promising strategy for developing effective TBEV vaccines.
• Candidate mRNA vaccines demonstrated significant immunogenicity and broad cross-protective efficacy against diverse TBEV strains.
• The study provides a strong foundation for the development of next-generation TBEV vaccines utilizing mRNA technology.