Definitive toxicology and biodistribution study of a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 (HIV-1) vaccine in rabbits.
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.
Pal
Ranajit
R
Department of Cell Biology, Advanced BioScience Laboratories, 5510 Nicholson Lane, Kensington, MD 20895, USA. Ranajit.Pal@ablinc.com
Yu
Qiao
Q
Wang
Shixia
S
Kalyanaraman
V S
VS
Nair
B C
BC
Hudacik
Lauren
L
Whitney
Stephen
S
Keen
Timothy
T
Hung
Chia-Ling
CL
Hocker
Lindsey
L
Kennedy
Jeffrey S
JS
Markham
Phillip
P
Lu
Shan
S
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
D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA