Beicht et al.
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;14:1177324. doi:10.3389/fimmu.2023.1177324

Currently available TBE vaccines are inactivated whole virus vaccines and their immunogenicity and protectivity are mainly based on glycoprotein E.

The nonstructural protein 1 (NS1) is found on the cell surface of TBE virus-infected cells and can be secreted into extracellular space (see, e.g., Snapshot week 37/2023). It was shown that NS1 is immunogenic and can partially protect mice against lethal challenge. The immunogenicity and protective efficacy have recently been analyzed when NS1 was expressed by neuraminidase-deficient influenza A virus (IAV) or by Modified Vaccinia virus Ankara (MVA) to yield MVA-NS1. In the IAV system, NS1 was fused in frame to the N-terminal part of the neuraminidase gene of strain PR8 to yield IAV-NS1.

To test the immunogenicity of the recombinant NS1 vector constructs, mice were vaccinated twice at a 4-week interval with the same construct or with a heterologous prime/boost regimen (IAV-NS1/MVA-NS1). Controls were vaccinated with the vector alone, FSME-IMMUN or PBS. Mice vaccinated with IAV-NS1 or MVA-NS1 developed NS1-specfic antibodies already after a single immunization. A booster dose enhanced the antibody titers, and with the heterologous prime/boost regimen, significant higher titers were achieved, but no neutralizing antibodies. The control vaccination with FSME-IMMUN did not induce NS1 specific antibodies, but high neutralizing antibodies.

In INF-γ ELISpot assays, NS1-specific T-cell response was detected, and this was higher in the heterologous prime/boost regimen. In challenge experiments with the Neudörfl TBE virus strain, mice were partially protected (33%–50%). The protected mice developed no clinical signs and had no loss of body weight. Heterologous prime/boost vaccination reduced the virus load in the spleen, reduced macroscopic abnormalities in the gastrointestinal tract, and reduced the replication in the brain.

These results are in agreement with previous studies that NS1-based vaccine preparations can partially protect mice against a lethal challenge with TBE virus. The reduced viral loads in the periphery, CNS and intestine suggest that the induction of immunity to NS1 favors restriction of viral replication. The authors conclude that the use of NS1 as (additional) vaccine antigen may offer advantage over the use of glycoprotein E-based vaccines.

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