To Örebro University

Background: Tick-borne encephalitis (TBE) is a growing public health concern in Europe and Asia, driven by the increasing spread of the TBE virus (TBEV) and its tick vectors. Although current vaccines provide protection, their multi-dose schedule and reduced efficacy in the elderly contribute to occasional vaccine failures. This study aims to develop a novel TBE vaccine offering enhanced protection with fewer doses, focusing on mucosal immunization.Methods: Infectious clone of Langat virus (LGTV IC) was designed and rescued- in our laboratory. We assessed the safety and immunogenicity of the LGTV IC as a live-attenuated TBE vaccine platform in a murine model. Mice were vaccinated with LGTV IC via intranasal or intramuscular routes at low or high doses. We evaluated viremia,viral presence in cerebrospinal fluid, general health, and immune responses.Results: Intranasal immunization with LGTV IC induced strong immune responses. It elicited robust anti-TBEVIgG responses and strong TBEV NS3-specific IFN-γ and IL-2 production. Notably, low-dose intranasal immunization outperformed higher doses of both routes, inducing a more balanced and effective immune response. Low-dose intranasal administration was well tolerated, with no clinical signs, weight loss, or viral presence in the central nervous system. In contrast, intranasal immunization caused potential adverse effects atelevated doses.Conclusion: These findings support LGTV IC as a promising vaccine platform for TBE, with intranasal administration emerging as a putative safe, well-tolerated, and effective needle-free alternative to intramuscular injection when given at a low dose. Ongoing efforts are focused on further attenuating LGTV IC to enhance its safety profile for future applications.