Zhang et al.
A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy. Virol Sin. Published online July 30, 2026. doi:10.1016/j.virs.2026.07.010
All licensed TBE vaccines are so far based on inactivated whole-virus particles.
An NS1 trans-complementation platform has been applied to TBE vaccine design, generating replication-defective TBE virus particles with a deletion in the gene encoding the nonstructural protein 1 (NS1). In this system, viral replication is supported in trans by a helper cell line expressing NS1.
A TBE virus cDNA clone has been established with a large in-frame deletion (amino acids 4-298) of NS1 (TBEV-ΔNS1). The deleted NS1 function is provided in trans by a BHK cell line stably expressing heterologous NS1 from the Omsk hemorrhagic fever virus (BHKNS1). The heterologous NS1 trans-complementation platform has been validated as reliable and highly efficient. The BHKNS1 cell line can rescue the replication defect of TBEV-ΔNS1. TBEV-ΔNS1 stably maintains the NS1 deletion during serial passaging, without recombination or reversion to a replication-competent wild-type virus.
While ICR mice infected with wild-type virus became ill and died, no clinical manifestations or evidence of virulence were observed when mice were inoculated with TBEV-ΔNS1. Mice inoculated with a single dose of TBEV-ΔNS1 developed neutralizing antibodies, mounted a robust T-cell response, and were protected against a lethal challenge with wild-type virus (100% protection was observed at the higher dose of TBEV-ΔNS1).
In summary, this replication-defective virus shows a promising preclinical safety and efficacy profile as a potential TBE vaccine candidate and warrants further development.