Safety evaluation of GX-12. A new DNA vaccine for HIV infection in rodents.
Toxicity studies for the evaluation of the safety of GX-12, a naked DNA vaccine for the treatment of human immunodeficiency virus (HIV) infection, were performed in rodents. In a single dose intramuscular or intravenous toxicity study, animals were treated with up to 4000 micrograms/kg of GX-12. During the experimental period, no abnormalities in mortality, clinical finding, or body weight change were observed. For subacute toxicity study, GX-12 was administered intramuscularly once a week for thirteen weeks to rats at dosages of 0.250, 1000, or 4000 micrograms/kg. Throughout the experimental period, no dead animals, notable clinical signs, changes in body weight gain, or food and water consumptions were observed. Ophthalmic examination, urinalysis, hematology, and serum chemistry, revealed no abnormalities. In addition, there were no changes in gross findings, organ weight, and histological findings. Based on these results, the NOAEL was estimated to be excess of 4000 micrograms/kg. To assess the possible effects on the immune system, we investigated the induction of anti-DNA or anti-myosin autoantibodies in mice immunized and boosted with GX-12, and anti-GX-12 antibodies in rat serum obtained from the subacute toxicity study. GX-12 neither stimulated the production of anti-DNA or myosin autoantibodies nor induced the development of myositis or glomerulonephritis. Therefore, we concluded that GX-12 has no toxicity up to 4000 micrograms/kg in this rat model, which is 60 times higher than the expected human dose. Furthermore, given the limitations of this study, GX-12 neither initiated nor accelerated the development of systemic autoimmune responses.
Choi
Seul Min
SM
Research Laboratories, Dong-A Pharmaceutical Co. Ltd., Kiheung, Yongin, Kyunggi, Korea.
Lee
Dong Sop
DS
Son
Mi Kyung
MK
Sohn
Young Sung
YS
Kang
Kyung Koo
KK
Kim
Chae Young
CY
Kim
Byung Moon
BM
Kim
Won Bae
WB
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001323:Autoantibodies; D004247:DNA / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007273:Injections, Intramuscular; D008297:Male; D009218:Myosins / Q000276:immunology; D019055:No-Observed-Adverse-Effect Level; D051381:Rats; D017207:Rats, Sprague-Dawley; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects*
D016915:AIDS Vaccines; D001323:Autoantibodies; D019444:Vaccines, DNA; D004247:DNA; D009218:Myosins