title: Definitive toxicology and biodistribution study of a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 (HIV-1) vaccine in rabbits.
abstract: A toxicity and immunogenicity study, evaluating the safety of a polyvalent DNA prime/protein boost HIV-1 vaccine (DP6-001), was examined in rabbits. Animals were primed with a cocktail of six different DNA plasmids expressing five HIV-1 env genes and one gag gene followed by boosting with five gp120 proteins homologous to the DNA vaccines. The vaccine was shown to be immunogenic as evident from the induction of high-titered anti-Env and anti-Gag antibodies. There was an absence of detectable adverse effects on key toxicology parameters. Although plasmids persisted in the injection sites following single administration for 64 days, no evidence of integration into the host genomic DNA was observed. These studies demonstrate that a novel polyvalent DNA prime/protein boost vaccine lacks signs of toxicity and DNA integration in a rabbit model, and immunogenicity and toxicology data support clinical testing of the vaccine in humans.
authors.affiliation: Department of Cell Biology, Advanced BioScience Laboratories, 5510 Nicholson Lane, Kensington, MD 20895, USA. Ranajit.Pal@ablinc.com
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.forename: Qiao
authors.initials: Q
authors.lastname: Yu
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: V S
authors.initials: VS
authors.lastname: Kalyanaraman
authors.forename: B C
authors.initials: BC
authors.lastname: Nair
authors.forename: Lauren
authors.initials: L
authors.lastname: Hudacik
authors.forename: Stephen
authors.initials: S
authors.lastname: Whitney
authors.forename: Timothy
authors.initials: T
authors.lastname: Keen
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hung
authors.forename: Lindsey
authors.initials: L
authors.lastname: Hocker
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Phillip
authors.initials: P
authors.lastname: Markham
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007115:Immunization Schedule; D010957:Plasmids; D011817:Rabbits; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity
chemical_list: D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA