Background: Plasmid DNA vaccines have been tested in a variety of investigational clinical settings, and given alone, they have been weakly immunogenic in human trials. Various strategies have been used to improve the immunogenicity of DNA vaccines: i) Electroporation (EP) has been shown to be an efficient means to introduce DNA into cells.  The Ichor TriGridÔ Delivery System (TDS-IM) is an integrated fully automated administration device.

Method: We propose to conduct a Phase 1 randomized, placebo-controlled, double-blind clinical trial in HIV-uninfected healthy adult volunteers at low-risk for HIV infection to evaluate the safety, tolerability and immunogenicity of a fixed dose of the HIV-MAG pDNA encoding gag-pol, nef- tat-vif and env genes, co-administered with two dosage levels of plasmid human IL-12 (IL-12 pDNA) delivered IM/EP, followed or preceded by recombinant Ad35-GRIN/ENV HIV vaccine delivered IM.

The hypotheses tested for this prime-boost regimen are:

• The proposed prime-boost vaccine regimens will be safe.
• GENEVAX^® IL-12 co-administration with HIV-MAG will increase HIV vaccine specific responses.
• The Ad35 GRIN /ENV vaccine will boost HIV-specific CD4+ and CD8+ T-cells in a majority of vaccine recipients.
• HIV-MAG co-administered with GENEVAX^® IL-12 will boost HIV-specific immune responses induced by the Ad35-GRIN/ENV vaccine.

Study Population: The study population consists of healthy male or female adults aged 18-50 years at low risk for HIV infection, who are willing to undergo HIV testing, use an effective method of contraception, and who in the opinion of the investigator or designee, understand the study and provide written informed consent. Approximately 75 volunteers (60 vaccine recipients, 15 placebo recipients) who meet all eligibility criteria will be included in the study.