Kubinski et al.
Immunity to tick-borne encephalitis virus NS3 protein induced with a recombinant modified vaccinia virus Ankara fails to afford mice protection against TBEV infection
Vaccines. 2024;12(1):105. doi:10.3390/vaccines12010105

Current TBE vaccines are based on chemically inactivated virions. Their protection capacity is mainly based on the immunogenicity of glycoprotein E.

It has been shown that among the non-structural proteins (NS), NS1 can also contribute to protection in mice against lethal challenge with TBE virus, e.g. when recombinantly expressed by modified vaccinia virus Ankara (MVA) or when fused in-frame to the N-terminus of the neuraminidase gene of neuraminidase-deficient influenza virus (Snapshot week 38/2023).

Among the NS proteins, NS3 plays a central role in the replication cycle of flaviviruses and also in polyprotein processing, and it has triphosphatase activity. It has been shown that NS3 can induce T-cell responses. Therefore, it was tested if NS3 can have a protective potential when expressed by MVA and used for immunization of mice (MVA-NS3).

Mice immunized twice with MVA-NS3 developed non-neutralizing TBE specific antibodies and a specific T-cell response (in contrast to empty MVA vector). In contrast to mice vaccinated with a commercial TBE vaccine (FSME Immun), mice vaccinated with MVA-NS3 were not protected against a challenge with TBE virus strain Neudörfl and developed severe clinical signs. TBE virus replicated in the brain and spleen and showed macroscopical lesions in the gastrointestinal tract.

The authors concluded that NS3 is not a promising candidate of next-generation TBE vaccines.

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