Safety evaluation of GX-12, a new HIV therapeutic vaccine: investigation of integration into the host genome and expression in the reproductive organs.
AIDS is one of the greatest infectious disease threats to human health despite the extensive efforts made since the discovery of HIV in 1983. The use of plasmid DNA vaccination to elicit humoral and cell-mediated immune responses against HIV infection has produced promising results in animal and in human trials. However, there are several safety concerns about the use of a DNA vaccine, which include the possibility of integration into the host genome, adverse immunopathology, and anti-DNA autoantibody induction. In this study, we examined the potential integration and distribution of GX-12, a new therapeutic vaccine for HIV infection, at various times in muscles and reproductive organs of rats. Animals of both sexes were injected with GX-12 at the dose of 400 microg/animal i.m. once a week for 4 weeks, and host genome integration and tissue distribution were examined on day 1, 5, 15, 30 and 45 days after the final injection. A PCR-based assay revealed that GX-12 was not integrated into the host genome, nor expressed in reproductive organs at any time. These findings suggest that the risk of mutation or germline transmission due to GX-12 injection is negligible.
Kang
Kyung Koo
KK
Research Laboratories, Dong-A Pharmaceutical Co. Ltd., Yongin-shi, Kyunggi-do, Korea. kangkk@donga.co.kr
Choi
Seul Min
SM
Choi
Jae Hoon
JH
Lee
Dong Sup
DS
Kim
Chae Young
CY
Ahn
Byung Ok
BO
Kim
Byung Moon
BM
Kim
Won Bae
WB
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics*; D000818:Animals; D005260:Female; D005835:Genitalia / Q000821:virology*; D015658:HIV Infections / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007273:Injections, Intramuscular; D008297:Male; D009928:Organ Specificity; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics; D016662:Virus Integration
D016915:AIDS Vaccines; D019444:Vaccines, DNA