title: A live, attenuated recombinant West Nile virus vaccine.
abstract: West Nile (WN) virus is an important cause of febrile exanthem and encephalitis. Since it invaded the U.S. in 1999, >19,000 human cases have been reported. The threat of continued epidemics has spurred efforts to develop vaccines. ChimeriVax-WN02 is a live, attenuated recombinant vaccine constructed from an infectious clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes of 17D have been replaced by the corresponding genes of WN virus. Preclinical tests in monkeys defined sites of vaccine virus replication in vivo. ChimeriVax-WN02 and YF 17D had similar biodistribution but different multiplication kinetics. Prominent sites of replication were skin and lymphoid tissues, generally sparing vital organs. Viruses were cleared from blood by day 7 and from tissues around day 14. In a clinical study, healthy adults were inoculated with 5.0 log(10) plaque-forming units (PFU) (n = 30) or 3.0 log10 PFU (n = 15) of ChimeriVax-WN02, commercial YF vaccine (YF-VAX, n = 5), or placebo (n = 30). The incidence of adverse events in subjects receiving the vaccine was similar to that in the placebo group. Transient viremia was detected in 42 of 45 (93%) of ChimeriVax-WN02 subjects, and four of five (80%) of YF-VAX subjects. All subjects developed neutralizing antibodies to WN or YF, respectively, and the majority developed specific T cell responses. ChimeriVax-WN02 rapidly elicits strong immune responses after a single dose, and is a promising candidate warranting further evaluation for prevention of WN disease.
authors.affiliation: Acambis, 38 Sidney Street, Cambridge, MA 02139, USA. tom.monath@acambis.com
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Niranjan
authors.initials: N
authors.lastname: Kanesa-Thasan
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: Myers
authors.forename: Richard
authors.initials: R
authors.lastname: Nichols
authors.forename: Alison
authors.initials: A
authors.lastname: Deary
authors.forename: Karen
authors.initials: K
authors.lastname: McCarthy
authors.forename: Casey
authors.initials: C
authors.lastname: Johnson
authors.forename: Thomas
authors.initials: T
authors.lastname: Ermak
authors.forename: Sunheang
authors.initials: S
authors.lastname: Shin
authors.forename: Juan
authors.initials: J
authors.lastname: Arroyo
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.forename: Sharone
authors.initials: S
authors.lastname: Green
authors.forename: Philip
authors.initials: P
authors.lastname: Bedford
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology / Q000633:toxicity; D014765:Viral Vaccines / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D014779:Virus Replication; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D015005:Yellow fever virus / Q000235:genetics
chemical_list: D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines