ChimeriVax is a live, attenuated recombinant virus constructed from
yellow fever (YF) 17D in which the envelope
protein genes of YF 17D are replaced with the corresponding genes of another flavivirus. A
ChimeriVax vaccine was developed against
Japanese encephalitis (JE). A randomized, double-blind, outpatient study was conducted to compare the safety and immunogenicity of
ChimeriVax-JE and YF 17D. Six YF immune and six non-immune adults were randomized to receive a single SC inoculation of
ChimeriVax-JE (5log(10)PFU),
ChimeriVax-JE (4log(10)PFU) or YF-VAX((R)) (5log(10)PFU). Mild, transient
injection site reactions and flu-like symptoms were noted in all treatment groups, with no significant difference between the groups. Nearly all subjects inoculated with
ChimeriVax-JE at both dose levels developed a transient, low-level
viremia which was similar in magnitude and duration to that following YF-VAX).
Neutralizing antibody seroconversion rates to
ChimeriVax-JE was 100% in the high and low dose groups in both naïve and YF immune subjects; seroconversion to wild-type JE strains was similar or lower than to the homologous (
vaccine) virus. Mean
neutralizing antibody responses were higher in the
ChimeriVax-JE high dose groups (naïve subjects LNI 1.55, PRNT(50) 254; YF immune subjects LNI 2.23, PRNT(50) 327) than in the low dose groups (naïve subjects 1.38, PRNT(50) 128; YF immune subjects LNI 1.62, PRNT(50) 270). JE antibody levels were higher in YF immune than in naïve subjects, dispelling concerns about anti-vector immunity. The safety and immunogenicity profile of
ChimeriVax-JE
vaccine appears to be similar to that of YF 17D. The new
vaccine holds promise for prevention of JE in travelers and residents of endemic countries. The
ChimeriVax technology platform is being exploited for development of new
vaccines against
dengue and West Nile.