"Prime-Boost" Vaccine Schedule for Prevention of HIV Infection

Study Design: This is a Phase I randomized study to examine safety and tolerability of, as well as immune response to, a schedule of 3 HIV DNA plasmid vaccinations followed by one HIV adenoviral vector vaccine (rAd) booster. The hypotheses are that: 1) this regimen will be safe for human administration and elicit immune responses to HIV-1; 2) Biojector and Needle/Syringe are both safe to use for IM injection of the DNA vaccine and 3) subjects with both low and high pre-existing adenovirus serotype 5 antibody (Ad5Ab) titer will have a boost in immune response to HIV-1 peptides following the Ad booster vaccination. In this study equal numbers of subjects with high and low Ad5Ab titers will be randomized to receive DNA vaccinations by either needle and syringe (N/S) or by Biojector and then to receive either 1010 PU or 1011 PU rAd booster vaccination in a factorial design. The primary objective is to evaluate the safety and tolerability in humans of the prime-boost vaccination regimen. Secondary objectives are related to evaluation of the immunogenicity of the DNA vaccine when administered by N/S or Biojector, the immunogenicity of the Ad vaccine at two different doses in subjects with high and low pre-enrollment titers of Ad5Ab, the development of adenovirus serotype 5 neutralizing antibody and the social impact of participating in an HIV-1 vaccine trial. Exploratory evaluations of the immunogenicity of the prime-boost regimen are also planned. The preliminary results may serve as the basis for designing studies to provide more definitive answers to questions about method of administration and effect of pre-enrollment Ad5Ab titer on safety of and immune response to the rAd booster vaccination. Product Description: VRC-HIVDNA016-00-VP is composed of 6 closed, circular DNA plasmids that are each 16.67% (by weight) of the vaccine. Each of the 6 plasmids in this vaccine expresses a single gene product. Plasmids VRC 4401, VRC 4409 and VRC 4404 are designed to express clade B HIV-1 Gag, Pol and Nef, respectively. VRC 5736, VRC 5737, and VRC 5738 are designed to express HIV-1 Env glycoprotein from clade A, clade B, and clade C, respectively. Vaccine vials will be supplied at 4 mg/mL. DNA vaccinations will be 1 mL of vaccine administered intramuscularly using either N/S or the Biojector 2000 Needle-Free Injection Management System. VRC-HIVADV014-00-VP is a recombinant product composed of four non-replicating adenoviral vectors (in a 3:1:1:1 ratio) that code for HIV-1 Gag/Pol polyproteins from clade B and HIV-1 Env glycoproteins from clades A, B, and C. All rAd injections will be administered by N/S. Subjects: Forty healthy adult volunteers, 18 to 50 years old; 20 subjects with low Ad5Ab (1:500) and 20 subjects with high Ad5Ab (greater than 1:500). Study Plan: Forty subjects will be randomized in a 1:1 ratio to receive the same vaccination schedule but by two different methods of intramuscular administration (N/S or Biojector), as shown in the schema. The rAd boost will also be randomized to be either 1010 PU or 1011 PU in 1:1 ratio. The rAd boost dosage will be blinded until 6 weeks of safety and immunogenicity evaluations after the rAd boost are completed for all subjects.