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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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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author Naveed Asghar
Rita Jaafar
Anna Valko
Olivia Merinder
Karl Ljungberg
Carl Mårten Lindqvist
Magnus Johansson
author_facet Naveed Asghar
Rita Jaafar
Anna Valko
Olivia Merinder
Karl Ljungberg
Carl Mårten Lindqvist
Magnus Johansson
author_sort Naveed Asghar
collection DOAJ
description 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.
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id doaj-art-7ebb5e9b529d415f96d781e1a12b9ec7
institution OA Journals
issn 2948-1767
language English
publishDate 2025-05-01
publisher Nature Portfolio
record_format Article
series npj Viruses
spelling doaj-art-7ebb5e9b529d415f96d781e1a12b9ec72025-08-20T02:34:06ZengNature Portfolionpj Viruses2948-17672025-05-013111210.1038/s44298-025-00129-6Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccineNaveed Asghar0Rita Jaafar1Anna Valko2Olivia Merinder3Karl Ljungberg4Carl Mårten Lindqvist5Magnus Johansson6School of Medical Sciences, Faculty of Medicine and Health, Örebro UniversitySchool of Medical Sciences, Faculty of Medicine and Health, Örebro UniversitySchool of Medical Sciences, Faculty of Medicine and Health, Örebro UniversityScantox SwedenInternational Vaccine Institute, Europe Regional OfficeClinical Genomics, Faculty of Medicine and Health, Örebro UniversitySchool of Medical Sciences, Faculty of Medicine and Health, Örebro UniversityAbstract 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.https://doi.org/10.1038/s44298-025-00129-6
spellingShingle Naveed Asghar
Rita Jaafar
Anna Valko
Olivia Merinder
Karl Ljungberg
Carl Mårten Lindqvist
Magnus Johansson
Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
npj Viruses
title Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
title_full Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
title_fullStr Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
title_full_unstemmed Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
title_short Development of Langat virus infectious clones as a platform for live-attenuated tick-borne encephalitis vaccine
title_sort development of langat virus infectious clones as a platform for live attenuated tick borne encephalitis vaccine
url https://doi.org/10.1038/s44298-025-00129-6
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