A replication-defective tick-borne encephalitis virus generated by NS1 <i>trans</i>-complementation confers robust protective efficacy

Ji Zhang; Qiu-Yan Zhang; Zhe-Rui Zhang; Ya-Nan Zhang; Hong-Qing Zhang; Cheng-Lin Deng; Bo Zhang

doi:10.1016/j.virs.2026.07.010

August 2026

Citation: Ji Zhang, Qiu-Yan Zhang, Zhe-Rui Zhang, Ya-Nan Zhang, Hong-Qing Zhang, Cheng-Lin Deng, Bo Zhang. A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy .VIROLOGICA SINICA, 2026, 41(4) : 937-946. http://dx.doi.org/10.1016/j.virs.2026.07.010

A replication-defective tick-borne encephalitis virus generated by NS1 trans-complementation confers robust protective efficacy

State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Wuhan 430071, China

Corresponding author: Cheng-Lin Deng, dengcl@wh.iov.cn
Bo Zhang, zhangbo@wh.iov.cn
Received Date: 04 January 2026
Accepted Date: 28 July 2026
Available online: 30 July 2026

Abstract

Tick-borne encephalitis virus (TBEV) poses a severe threat to public health, causing neurological disorders with high morbidity and mortality in endemic regions. Therefore, developing safe and effective strategies for TBEV vaccines has long been a focus of attention. Herein, leveraging our well-established NS1 trans-complementation platform, we successfully constructed a high-titer replication-defective TBEV (TBEV-△NS1) using the BHK-21 cell line stably expressing Omsk hemorrhagic fever virus (OHFV) NS1 (designated BHK_NS1). Retention of the NS1 deletion in TBEV-△NS1 was confirmed by continuous passaging in BHK_NS1 cells, as no replicative virus was detected in naive BHK-21 cells. The safety profile of TBEV-△NS1 was further validated, as administration of a high dose of TBEV-△NS1 to ICR mice did not induce any clinical symptoms. Notably, TBEV-△NS1 conferred complete protection against lethal wild-type (WT) TBEV challenge in ICR mice, whereas non-immunized control mice exhibited 100% mortality, significant weight loss, and viremia. This protective efficacy is tightly correlated with robust humoral and cellular immune responses, as demonstrated by the induction of high titers of TBEV-specific IgG, neutralizing antibodies, and IFN-γ-secreting CD8⁺ T cells following a single immunization. Collectively, our findings provide a proof-of-concept for the NS1 trans-complementation platform in TBEV vaccine development.
- Tick-borne encephalitis virus (TBEV)
- , NS1
- , Trans-complementation strategy
- , Vaccine

Electronic Supplementary Material

10.1016j.virs.2026.07.010-ESM.docx
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