title: Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation.
abstract: ADVAX is a DNA-based candidate HIV vaccine that was safe but weakly immunogenic when delivered intramuscularly (IM) in humans. Studies were performed in animal models to determine whether an alternative delivery method, in vivo electroporation (EP), could improve the immunogenicity of ADVAX while maintaining an acceptable safety profile. Immunization of mice with ADVAX with or without EP at weeks 0, 3, and 6, revealed significantly higher gamma interferon ELISpot responses to all antigens in the EP groups. Antigen-specific CD4+ and CD8+ T cell responses, as quantified by intracellular cytokine staining, both improved significantly with EP. Evaluation of repeat-dose toxicity of ADVAX-EP in rabbits did not reveal any safety concerns. Biodistribution studies of ADVAX delivered IM and with EP in rats indicated that the vaccine was localized predominantly to the administration site in both groups. PCR-based quantitation of residual plasmid at Day 60 indicated that the potential for integration events into the host genome was low for both IM and EP delivery. Taken together, these data supported the clinical development of ADVAX delivered with EP in human volunteers.
authors.affiliation: Ichor Medical Systems, 6310 Nancy Ridge Drive, Suite 107, San Diego, CA 92121, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Dolter
authors.forename: Claire F
authors.initials: CF
authors.lastname: Evans
authors.forename: Barry
authors.initials: B
authors.lastname: Ellefsen
authors.forename: Juwan
authors.initials: J
authors.lastname: Song
authors.forename: Mar
authors.initials: M
authors.lastname: Boente-Carrera
authors.forename: Roselle
authors.initials: R
authors.lastname: Vittorino
authors.forename: Talia J
authors.initials: TJ
authors.lastname: Rosenberg
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.forename: Sandhya
authors.initials: S
authors.lastname: Vasan
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000493:pharmacokinetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018274:Electroporation / Q000379:methods*; D005260:Female; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology* / Q000493:pharmacokinetics
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma