Clinical proof of principle for ChimeriVax™: recombinant live, attenuated vaccines against flavivirus infections

Abstract

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 (5 log 10 PFU), ChimeriVax™-JE (4 log 10 PFU) or YF-VAX ® (5 log 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 naı̈ve 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 (naı̈ve subjects LNI 1.55, PRNT 50 254; YF immune subjects LNI 2.23, PRNT 50 327) than in the low dose groups (naı̈ve 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 naı̈ve 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.