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

ChimeriVax(TM) 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(TM) vaccine was developed against Japanese encephalitis (JE). A randomized, double-blind, outpatient study was conducted to compare the safety and immunogenicity of ChimeriVax(TM)-JE and YF 17D. Six YF immune and six non-immune adults were randomized to receive a single SC inoculation of ChimeriVax(TM)-JE (5log(10) PFU), ChimeriVax(TM)-JE (4 log(10) PFU) or YF-VAX((R)) (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(TM)-JE at both dose levels developed a transient, low-level viremia which was similar in magnitude and duration to that following YF-VAX((R)). Neutralizing antibody seroconversion rates to ChimeriVax(TM)-JE was 100% in the high and low dose groups in both naive 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(TM)-JE high dose groups (naive subjects LNI 1.55, PRNT50 254; YF immune subjects LNI 2.23, PRNT50 327) than in the low dose groups (naive subjects 1.38, PRNT50 128; YF immune subjects LNI 1.62, PRNT50 270). JE antibody levels were higher in YF immune than in naive subjects, dispelling concerns about anti-vector immunity. The safety and immunogenicity profile of ChimeriVax(TM)-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(TM) technology platform is being exploited for development of new vaccines against dengue and West Nile. (C) 2002 Elsevier Science Ltd. All rights reserved.