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

F. Guirakhoo, Z. X. Zhang, T. J. Chambers, S. Delagrave, J. Arroyo, Alan Barrett, T. P. Monath

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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 (ChimeriVaxJE 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 ≥103 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.

Original languageEnglish (US)
Pages (from-to)363-372
Number of pages10
JournalVirology
Volume257
Issue number2
DOIs
StatePublished - May 10 1999

Fingerprint

Japanese Encephalitis Virus
Japanese Encephalitis
Yellow Fever
Attenuated Vaccines
Yellow Fever Vaccine
Cell Culture Techniques
Viruses
Genes
Flavivirus
Brain
Clone Cells
ChimeriVax
Phenotype

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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, Z. X.; Chambers, T. J.; Delagrave, S.; Arroyo, J.; Barrett, Alan; Monath, T. P.

In: Virology, Vol. 257, No. 2, 10.05.1999, p. 363-372.

Research output: Contribution to journalArticle

@article{f5de13a0c95248ff96da2f842256bb29,
title = "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",
abstract = "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 (ChimeriVaxJE 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 ≥103 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.",
author = "F. Guirakhoo and Zhang, {Z. X.} and Chambers, {T. J.} and S. Delagrave and J. Arroyo and Alan Barrett and Monath, {T. P.}",
year = "1999",
month = "5",
day = "10",
doi = "10.1006/viro.1999.9695",
language = "English (US)",
volume = "257",
pages = "363--372",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - 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

AU - Guirakhoo, F.

AU - Zhang, Z. X.

AU - Chambers, T. J.

AU - Delagrave, S.

AU - Arroyo, J.

AU - Barrett, Alan

AU - Monath, T. P.

PY - 1999/5/10

Y1 - 1999/5/10

N2 - 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 (ChimeriVaxJE 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 ≥103 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.

AB - 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 (ChimeriVaxJE 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 ≥103 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.

UR - http://www.scopus.com/inward/record.url?scp=0033541937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033541937&partnerID=8YFLogxK

U2 - 10.1006/viro.1999.9695

DO - 10.1006/viro.1999.9695

M3 - Article

VL - 257

SP - 363

EP - 372

JO - Virology

JF - Virology

SN - 0042-6822

IS - 2

ER -