title: Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV.
abstract: Immunization involving a DNA vaccine prime followed by an adenovirus type 5 (Ad5) boost elicited a protective immune response against SHIV challenge in monkeys. However, the hepatocellular tropism of Ad5 limits the safety of this viral vector. This study examines the safety and immunogenicity of a replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35) in BALB/c mice and rhesus monkeys. This novel Ad5/35 vector showed minimal hepatotoxicity after intramuscular administration with the novel Ad5/35 vector. In addition, an Ad5/35 vector expressing HIV Env gp160 protein (Ad5/35-HIV) generated strong HIV-specific immune responses in both animal models. Priming with a DNA vaccine followed by Ad5/35-HIV boosting yielded protection against a gp160-expressing vaccinia virus challenge in BALB/c mice. The Ad5/35-HIV vector was significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector. These findings indicate that an Ad5/35 vector-based HIV vaccine may be of considerable value for clinical use.
authors.affiliation: Department of Molecular Biodefense Research, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: K-Q
authors.initials: KQ
authors.lastname: Xin
authors.forename: N
authors.initials: N
authors.lastname: Jounai
authors.forename: K
authors.initials: K
authors.lastname: Someya
authors.forename: K
authors.initials: K
authors.lastname: Honma
authors.forename: H
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: S
authors.initials: S
authors.lastname: Naganawa
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: T
authors.initials: T
authors.lastname: Hayakawa
authors.forename: S
authors.initials: S
authors.lastname: Saha
authors.forename: F
authors.initials: F
authors.lastname: Takeshita
authors.forename: K
authors.initials: K
authors.lastname: Okuda
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: D M
authors.initials: DM
authors.lastname: Klinman
authors.forename: K
authors.initials: K
authors.lastname: Okuda
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000008:administration & dosage; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007114:Immunization / Q000379:methods*; D007117:Immunization, Secondary; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009500:Neutralization Tests; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014616:Vaccinia virus / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics; D018406:Virus Physiological Phenomena
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D019444:Vaccines, DNA; D014764:Viral Proteins