title: Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus--poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans.
abstract: A controlled, randomized, double-blind clinical trial evaluated whether two attenuated recombinant poxviruses with identical Japanese encephalitis virus (JEV) gene insertions, NYVAC-JEV and ALVAC-JEV, were safe and immunogenic in volunteers. Groups of 10 volunteers distinguished by vaccinia immune status received two doses of each vaccine. The vaccines appeared to be equally safe and well tolerated in volunteers, but more reactogenic than licensed formalin-inactivated JE and placebo vaccines given as controls. NYVAC-JEV and ALVAC-JEV vaccine recipients had frequent occurrence of local warmth, erythema, tenderness, and/or arm pain after vaccination. There was no apparent effect of vaccinia immune status on frequency or magnitude of local and systemic reactions. NYVAC-JEV elicited antibody responses to JEV antigens in recipients but ALVAC-JEV vaccine poorly induced antibody responses. However, NYVAC-JEV vaccine induced neutralizing antibody responses only in vaccinia-nonimmune recipients while vaccinia-immune volunteers failed to develop protective antibodies (5/5 vs. 0/5 seroconversion, p<0.01). These data suggest that preexisting immunity to poxvirus vector may suppress antibody responses to recombinant gene products.
authors.affiliation: Department of Virus Diseases, DCD&I, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, MD 20910, Silver Spring, USA.
authors.forename: N
authors.initials: N
authors.lastname: Kanesa-thasan
authors.forename: J J
authors.initials: JJ
authors.lastname: Smucny
authors.forename: C H
authors.initials: CH
authors.lastname: Hoke
authors.forename: D H
authors.initials: DH
authors.lastname: Marks
authors.forename: E
authors.initials: E
authors.lastname: Konishi
authors.forename: I
authors.initials: I
authors.lastname: Kurane
authors.forename: D B
authors.initials: DB
authors.lastname: Tang
authors.forename: D W
authors.initials: DW
authors.lastname: Vaughn
authors.forename: P W
authors.initials: PW
authors.lastname: Mason
authors.forename: R E
authors.initials: RE
authors.lastname: Shope
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics; D004311:Double-Blind Method; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000276:immunology*; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control; D004890:Erythema / Q000209:etiology; D005822:Genetic Vectors; D006801:Humans; D009500:Neutralization Tests; D011212:Poxviridae / Q000235:genetics* / Q000276:immunology*; D012449:Safety; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D014615:Vaccinia / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines