Background

 DNA-based vaccines have been weakly immunogenic as stand alone vaccines in humans. Delivery of DNA-based vaccines via in vivo electroporation (EP) significantly enhances humoral and cellular immunogenicity over standard intramuscular injection in animal models. We are conducting the first clinical trial of a DNA-based HIV-1 vaccine delivered via EP in healthy HIV-seronegative volunteers.

 

 

 Methods

 Forty healthy individuals aged 18-60, at low risk for HIV-1, are being enrolled into this study. Vaccinations are administered at weeks 0 and 8. Eight volunteers per dosage group (low: 0.2mg; mid: 1.0mg; high: 4.0mg) receive ADVAX via EP with the TriGrid™ Delivery System, while eight volunteers receive saline placebo via EP, in a randomized double-blinded design. An additional eight volunteers receive standard intramuscular vaccination with high dose ADVAX (4.0mg). Volunteers are followed for safety, tolerability, and immunogenicity for 14 months.

 

 

 Results

 Enrollment of the low and mid dosage groups is complete (n=26). Twenty one volunteers have been vaccinated with ADVAX or placebo by EP; five have received ADVAX IM. Ten of ten volunteers have received the second vaccination at week 8. ADVAX or placebo administered by EP has been safe, with no severe local or systemic reactogenicity or serious adverse events to date. Discomfort immediately following EP was significantly reduced after 30 minutes, as assessed by standard tolerability questionnaires. After 31 EP procedures, surveys indicate 97% would accept EP for vaccination against a life-threatening infection such as HIV, while 81% found EP acceptable for vaccination against less severe infections such as influenza. Humoral and cellular immunogenicity assessments are underway.

 

 

 Conclusions

 To date, in vivo electroporation appears safe, well tolerated and acceptable in healthy volunteers.