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

Thomas P Monath; Farshad Guirakhoo; Richard Nichols; Sutee Yoksan; Robert Schrader; Chris Murphy; Paul Blum; Stephen Woodward; Karen McCarthy; Danell Mathis; Casey Johnson; Philip Bedford

doi:10.1086/378356

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

J Infect Dis. 2003 Oct 15;188(8):1213-30. doi: 10.1086/378356. Epub 2003 Oct 3.

Authors

Thomas P Monath¹, Farshad Guirakhoo, Richard Nichols, Sutee Yoksan, Robert Schrader, Chris Murphy, Paul Blum, Stephen Woodward, Karen McCarthy, Danell Mathis, Casey Johnson, Philip Bedford

Affiliation

¹ Acambis Inc, Cambridge, Massachusetts, USA. [email protected].

PMID: 14551893
DOI: 10.1086/378356

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.

Publication types

Clinical Trial
Clinical Trial, Phase II
Randomized Controlled Trial

MeSH terms

Animals
Antibodies, Viral / blood
Antigens, Viral / immunology
Dose-Response Relationship, Drug
Double-Blind Method
Encephalitis Virus, Japanese / genetics
Encephalitis Virus, Japanese / immunology
Encephalitis, Japanese / prevention & control*
Encephalitis, Japanese / virology
Genetic Vectors
Humans
Immunization Schedule
Immunologic Memory
Japanese Encephalitis Vaccines / administration & dosage
Japanese Encephalitis Vaccines / adverse effects*
Japanese Encephalitis Vaccines / immunology*
Mice
Neutralization Tests
Treatment Outcome
Vaccination
Vaccines, Attenuated / administration & dosage*
Vaccines, Attenuated / adverse effects
Vaccines, Attenuated / immunology
Vaccines, Inactivated
Viral Vaccines / administration & dosage
Viral Vaccines / adverse effects*
Viral Vaccines / genetics
Viral Vaccines / immunology*
West Nile Virus Vaccines
Yellow Fever Vaccine / administration & dosage
Yellow Fever Vaccine / adverse effects*
Yellow Fever Vaccine / genetics
Yellow Fever Vaccine / immunology*
Yellow fever virus / genetics

Substances

Antibodies, Viral
Antigens, Viral
ChimeriVax
Japanese Encephalitis Vaccines
Vaccines, Attenuated
Vaccines, Inactivated
Viral Vaccines
West Nile Virus Vaccines
Yellow Fever Vaccine