Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial

Abstract

We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 108 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

Trial registration: ClinicalTrials.gov NCT01407497.

Keywords: HIV; HIV-DNA; HIV-MVA; Mozambique; vaccine.

Conflict of interest statement

Richard Stout was an officer, employee and shareholder of Bioject, Inc., during the conduct of this trial. All other authors have no conflicts of interest.

Figures

FIG. 1.

Consort diagram.

FIG. 2.

Local and systemic solicited adverse events. Total number of reported events (A) after three HIV-DNA immunizations combined and (B) after two HIV-MVA boosts combined, in the lower dose (600 μg) and higher dose (1,200 μg) HIV-DNA recipients and placebos.

FIG. 3.

HIV-specific IFN-γ ELISpot responses. IFN-γ ELISpot responses in vaccinees after stimulation with Gag DNA, Gag CMDR, Env CMDR, and Pol CMDR peptide pools (A) 2 weeks after the third HIV-DNA immunization, (B) 2 weeks after the first HIV-MVA vaccination, and (C) 2 weeks after the second HIV-MVA vaccination. The number of responders per number of evaluable vaccinees is given in brackets. The bars show median values. ELISpot responses were considered positive if the number of SFCs was >55 spots/million PBMCs and four times the background value. The dashed line is at 55 SFCs/million PBMCs. Responders are shown by filled symbols and nonresponders are shown by open symbols.

FIG. 4.

IFN-γ ELISpot responses by HIV-DNA priming groups. The magnitude of IFN-γ ELISpot responses to (A) Gag DNA and (B) Gag CMDR 2 weeks after the third HIV-DNA immunization, to (C) Gag and (D) Env 2 weeks after the first HIV-MVA vaccination, and to (E) Gag and (F) Env 2 weeks after the second HIV-MVA vaccination. Data are presented for each of the HIV-DNA priming groups. The number of responders per number of evaluable vaccinees is given in brackets. Median values are given by the bars. ELISpot responses were considered positive if the number of SFCs was >55 spots/million PBMCs and four times the background value. The dashed line is at 55 SFCs/million PBMCs. Responders are shown by filled symbols and nonresponders are shown by open symbols.

FIG. 5.

Binding antibody titers by HIV-DNA priming group. Binding antibody titers to (A) recombinant HIV-1 CN54 subtype C gp140 and to (B) native HIV-1IIIB subtype B gp160 4 weeks after the second HIV-MVA vaccination. All evaluable vaccinees were reactive. The magnitude of the responses in the lower and higher HIV-DNA dose recipients is shown. The median titers are given in brackets. The Mann–Whitney U-test was used for comparisons.