Development and characterization of chimera of yellow fever virus vaccine strain and Tick-Borne encephalitis virus

• Published in: PloS one Vol. 18; no. 5; p. e0284823
• Main Authors: Kuznetsova, Nadezhda, Siniavin, Andrei, Butenko, Alexander, Larichev, Victor, Kozlova, Alina, Usachev, Evgeny, Nikiforova, Maria, Usacheva, Olga, Shchetinin, Alexey, Pochtovyi, Andrei, Shidlovskaya, Elena, Odintsova, Alina, Belyaeva, Elizaveta, Voskoboinikov, Aleksander, Bessonova, Arina, Vasilchenko, Lyudmila, Karganova, Galina, Zlobin, Vladimir, Logunov, Denis, Gushchin, Vladimir, Gintsburg, Alexander
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.05.2023
• Subjects: Animals; Antibodies; Arachnids; Biology and Life Sciences; Care and treatment; Cell culture; Central nervous system; Cloning; Complications and side effects; Cytomegalovirus; Dengue fever; Diagnosis; Encephalitis; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Fever; Genomes; Humans; Hybrid structures; Immunoglobulins; Invasiveness; Mammalian cells; Mammals; Medicine and Health Sciences; Mice; Neurotropism; Neurovirulence; Pathogens; Research and Analysis Methods; Severe acute respiratory syndrome coronavirus 2; Tick-borne encephalitis; Vaccines; Vector-borne diseases; Vectors (Biology); Viral Vaccines; Viruses; West Nile virus; Yellow fever; Yellow Fever Vaccine - genetics; Yellow fever virus - genetics; Zika virus; Russia; United Kingdom > UK; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0284823

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC, the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain, chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.