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

• Published in: Virology (New York, N.Y.) N.Y.), 1999-05, Vol.257 (2), p.363-372
• Main Authors: Guirakhoo, F., Zhang, Z.-X., Chambers, T.J., Delagrave, S., Arroyo, J., Barrett, A.D.T., Monath, T.P.
• Format: Article
• Language: English
• Subjects: Animals; Brain - virology; Cell Line; Cercopithecus aethiops; Disease Models, Animal; Encephalitis Virus, Japanese - genetics; Encephalitis Virus, Japanese - immunology; Encephalitis, Japanese - prevention & control; Genes, Viral; Genetic Vectors - genetics; Genetic Vectors - physiology; Humans; Japanese encephalitis virus; Macaca mulatta; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Recombination, Genetic; Sequence Analysis, DNA; Vaccines, Attenuated - immunology; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vero Cells; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - genetics; Viral Vaccines - immunology; Virus Replication; Yellow fever virus; Yellow fever virus - genetics; Yellow fever virus - growth & development; Yellow fever virus - physiology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1999.9695

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 log10plaque 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 ≥103pfu 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.