Kubinski et al.
A recombinant Modified Vaccinia virus Ankara expressing prME of tick-borne encephalitis virus affords mice full protection against TBEV infection
Front Immunol. 2023;14:1182963. doi:10.3389/fimmu.2023.1182963

Various TBE vaccines (inactivated whole virus preparations adsorbed to aluminum hydroxide) which are highly effective have been licensed. However, vaccine breakthrough infections are reported in a low percentage of fully vaccinated individuals. Therefore, research on alternative TBE vaccines is ongoing, and recently a recombinant TBE vaccine based on Modified Vaccinia virus Ankara (MVA) has been evaluated for immunogenicity and protectivity in mice. MVA is highly attenuated to human cells, and the safety and immunogenicity of MVA-based vaccines against a variety of viral pathogens has been demonstrated in clinical trials.

The pre-membrane prM glycoprotein and the glycoprotein E (gE) gene sequences of TBE virus strain Neudörfl were introduced into the MVA vector by homologous recombination resulting in MVA-prME. Immunization of mice with MVA-prME (or FSME-IMMUN for control) was well tolerated, and after two injections, neutralizing antibodies were induced (but not after mock immunization with MVA). In addition, T cell response was shown to various peptide pools by IFN-g ELISpot assays.

After two-fold immunization with MVA-prME (or with FSME-IMMUN), mice were protected against a lethal challenge dose with TBE virus strain Neudörfl. All PBS and MVA control mice developed clinical signs and displayed weight loss.

Vaccination with MVA-prME reduced viral load in the spleen, central nervous system and gastrointestinal tract and prevented pathological alterations after challenge with virus.

In summary, MVA-prME showed to be a highly promising approach as an alternative TBE vaccine. MVA-prME was well tolerated in mice and induced a strong neutralizing antibody response comparable with the licensed TBE vaccine FSME-IMMUN. In addition, gE-specific CD4+ and CD8+ T cell responses were induced, which was not observed after immunization with FSME-IMMUN and which correlated with clearance of infection.

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