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.