Chimeric Langat/Dengue Viruses Protect Mice from Heterologous Challenge with the Highly Virulent Strains of Tick-Borne Encephalitis Virus

Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in mosquito cell culture were completely attenuated in SCID...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2000-08, Vol.274 (1), p.26-31
Main Authors: Pletnev, Alexander G., Karganova, Galina G., Dzhivanyan, Tatiana I., Lashkevich, Vasilii A., Bray, Michael
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Animals
Cercopithecus aethiops
Dengue Virus - genetics
Dengue Virus - immunology
Dengue virus 4
Encephalitis Viruses, Tick-Borne - genetics
Encephalitis Viruses, Tick-Borne - immunology
Encephalitis Viruses, Tick-Borne - pathogenicity
Encephalitis, Tick-Borne - immunology
Encephalitis, Tick-Borne - prevention & control
Female
Flavivirus
Genetic Vectors - genetics
Genetic Vectors - immunology
Humans
Langat virus
Mice
Mice, Inbred BALB C
Mice, SCID
Tick-borne encephalitis virus
Vaccines, Synthetic - genetics
Vaccines, Synthetic - immunology
Vero Cells
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Viral Vaccines - genetics
Viral Vaccines - immunology
Virulence
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Description
Summary:Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in mosquito cell culture were completely attenuated in SCID mice but still capable of providing protection against LGT. To develop the chimeras into vaccine candidates, we adapted them to replicate efficiently in simian Vero cells, a satisfactory substrate for human vaccines. The adapted chimeras remained completely attenuated for SCID mice and, significantly, provided protection in immunocompetent mice against tick-borne encephalitis virus, the most virulent of the tick-borne flaviviruses.
ISSN:0042-6822
1096-0341
DOI:10.1006/viro.2000.0426