title: Chimeric live, attenuated vaccine against Japanese encephalitis (ChimeriVax-JE): phase 2 clinical trials for safety and immunogenicity, effect of vaccine dose and schedule, and memory response to challenge with inactivated Japanese encephalitis antigen.
abstract: ChimeriVax-JE is a live, attenuated vaccine against Japanese encephalitis, using yellow fever (YF) 17D vaccine as a vector. In a double-blind phase 2 trial, 99 adults received vaccine, placebo, or YF 17D vaccine (YF-VAX). ChimeriVax-JE was well tolerated, with no differences in adverse events between treatment groups. Viremias resulting from administration of ChimeriVax-JE and YF-VAX were of short duration and low titer; 82 (94%) of 87 subjects administered graded doses (1.8-5.8 log(10)) of ChimeriVax-JE developed neutralizing antibodies. A second dose, administered 30 days later, had no booster effect. Previous inoculation with YF did not interfere with ChimeriVax-JE, but there was a suggestion (not statistically significant) that ChimeriVax-JE interfered with YF-VAX administered 30 days later. A separate study explored immunological memory both in subjects who had received ChimeriVax-JE 9 months before and in ChimeriVax-JE-naive subjects challenged with inactivated mouse-brain vaccine (JE-VAX). Anamnestic responses were observed in preimmune individuals. ChimeriVax-JE appears to be a safe vaccine that provides protective levels of neutralizing antibody after a single dose.
authors.affiliation: Acambis Inc, Cambridge, Massachusetts, USA. tom.monath@acambis.com.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
authors.forename: Richard
authors.initials: R
authors.lastname: Nichols
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.forename: Robert
authors.initials: R
authors.lastname: Schrader
authors.forename: Chris
authors.initials: C
authors.lastname: Murphy
authors.forename: Paul
authors.initials: P
authors.lastname: Blum
authors.forename: Stephen
authors.initials: S
authors.lastname: Woodward
authors.forename: Karen
authors.initials: K
authors.lastname: McCarthy
authors.forename: Danell
authors.initials: D
authors.lastname: Mathis
authors.forename: Casey
authors.initials: C
authors.lastname: Johnson
authors.forename: Philip
authors.initials: P
authors.lastname: Bedford
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology; D004672:Encephalitis, Japanese / Q000517:prevention & control* / Q000821:virology; D005822:Genetic Vectors; D006801:Humans; D007115:Immunization Schedule; D007156:Immunologic Memory; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D016896:Treatment Outcome; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D015164:Vaccines, Inactivated; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D053060:West Nile Virus Vaccines; D022341:Yellow Fever Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D015005:Yellow fever virus / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; C445780:ChimeriVax; D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D053060:West Nile Virus Vaccines; D022341:Yellow Fever Vaccine