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        Immunogenicity, genetic stability, and protective efficacy of a 
        recombinant, chimeric yellow fever-Japanese encephalitis virus
        (ChimeriVax-JE) as a live, attenuated vaccine candidate against Japanese
        encephalitis.

           Guirakhoo F, Zhang ZX, Chambers TJ, Delagrave S, Arroyo J, Barrett AD,
           Monath TP
           OraVax, Inc., 38 Sidney Street, Cambridge, Massachusetts 02139, USA.
           [email protected]
           Virology 1999 May 10;257(2):363-72

        Yellow fever (YF) 17D vaccine virus, having a 60-year history of safe
        and effective use, is an ideal vector to deliver heterologous genes from
        other medically important flaviviruses. A chimeric YF/Japanese
        encephalitis (JE) virus (ChimeriVax-JE virus) was constructed by
        insertion of the premembrane and envelope (prME) genes of an attenuated
        human vaccine strain (SA14-14-2) of Japanese encephalitis (JE) virus
        between core and nonstructural (NS) genes of a YF 17D infectious clone.
        The virus grew to high titers in cell cultures and was not neurovirulent
        for 3- to 4-week-old mice at doses </=6 log10 plaque forming units (pfu)
        inoculated by the intracerebral (IC) route. In contrast, commercial YF
        17D vaccine was highly neurovirulent for weanling mice by the same
        route. Mice inoculated subcutaneously with one dose of >/=10(3) pfu of
        ChimeriVax-JE virus were solidly protected against intraperitoneal
        challenge with a virulent JE virus. Genetic stability of the chimera was
        assessed by sequential passages in cell cultures or in mouse brain. All
        attenuating residues and the avirulent phenotype were preserved after 18
        passages in cell cultures or 6 passages in mouse brains. Copyright 1999
        Academic Press.


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