Abstract
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.
Copyright 2000 Academic Press.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptation, Physiological
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Animals
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Chlorocebus aethiops
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Dengue Virus / genetics
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Dengue Virus / immunology*
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Encephalitis Viruses, Tick-Borne / genetics
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Encephalitis Viruses, Tick-Borne / immunology*
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Encephalitis Viruses, Tick-Borne / pathogenicity
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Encephalitis, Tick-Borne / immunology
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Encephalitis, Tick-Borne / prevention & control*
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Female
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Genetic Vectors / genetics
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Genetic Vectors / immunology
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Humans
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Mice
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Mice, Inbred BALB C
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Mice, SCID
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology*
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Vero Cells
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology*
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Viral Vaccines / genetics
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Viral Vaccines / immunology*
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Virulence
Substances
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Vaccines, Synthetic
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Viral Envelope Proteins
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Viral Vaccines
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prM protein, Flavivirus
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glycoprotein E, Flavivirus