Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine

Abstract Tick-borne encephalitis (TBE) is one of the most important tick-transmitted diseases in Europe and Asia. With no specific antiviral treatment available, vaccination remains the most effective protective strategy for TBE. Unlike currently available inactivated TBE vaccines that require repea...

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Bibliographic Details
Main Authors: Naveed Asghar, Rita Jaafar, Anna Valko, Olivia Merinder, Karl Ljungberg, Carl Mårten Lindqvist, Magnus Johansson
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:npj Viruses
Online Access:https://doi.org/10.1038/s44298-025-00129-6
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Summary:Abstract Tick-borne encephalitis (TBE) is one of the most important tick-transmitted diseases in Europe and Asia. With no specific antiviral treatment available, vaccination remains the most effective protective strategy for TBE. Unlike currently available inactivated TBE vaccines that require repeated boosters, live-attenuated vaccines could offer lifelong immunity with a single dose. Langat virus (LGTV) is a naturally attenuated strain of TBE virus (TBEV). In this study, we engineered and rescued four infectious clones (ICs) of LGTV using RNA- and DNA-based reverse genetics methods. The ICs rescued by DNA-based method showed higher genetic stability in cell culture. One of the ICs rescued by DNA-based method was further evaluated in vitro and in vivo, which exhibited growth kinetics and immune profile comparable to the LGTV strain in our laboratory. This reverse genetics platform will be utilized to introduce targeted mutations within the LGTV genome to develop a live-attenuated TBE vaccine.
ISSN:2948-1767