Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein

Abstract

Background The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. Methods In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1–uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. Results All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). Conclusions Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. Clinical Trials Registration South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27–0715–4917) and ClinicalTrials.gov (NCT02997969).

Antibody and cellular responses to HIV vaccine regimens with DNA plasmid as compared with ALVAC priming: An analysis of two randomized controlled trials

“…The 2 vaccine arms of HVTN 111 (i.e., DNA plasmid delivery by needle or by Biojector) were combined for the comparison of antibody responses between the 2 trials to maximize the sample size as no significant differences were seen between the 2 HVTN 111 vaccine arms [25]. Differences were seen in the cellular responses between the 2 arms of HVTN 111 [25], therefore cellular responses of the 2 individual vaccine arms of HVTN 111 were compared separately to the vaccine arm of HVTN 100.…”

“…Soshanguve [22]. HVTN 111 was a phase I randomized, controlled, double-blind trial at 3 community research sites in South Africa (Isipingo, Klerksdorp, and Tembisa), 1 site in Mbeya, Tanzania, and 1 site in Lusaka, Zambia [25].…”

“…Participants were followed for 12 months after the initial vaccination. Safety evaluations were performed as previously described [22,25]. Briefly, they included physical examinations and standard clinical chemistry and hematological tests, urine dipstick, as well as pregnancy tests for female participants.…”

“…In HVTN 111, a DNA plasmid vaccine encoding the same HIV-1 subtype C env strain as in the HVTN 100 ALVAC vector was delivered via either needle and syringe or via a Biojector needle-free device; Biojector administration had been shown previously to induce higher immunogenicity with a similar HIV-1 DNA plasmid vaccine [23,24]. The DNA plasmid vaccine was then boosted with the same subtype C Env proteins as in HVTN 100, and the same schedule was used in both studies [25].…”

The Case for Why Africa Should Host COVID-19 Candidate Vaccine Trials

“…Africa has a long history of, and considerable experience in, hosting and conducting vaccine trials [32], including phase 1 vaccine trials on a range of major diseases across the continent [33][34][35][36][37]. African scientists are also making valuable contributions to COVID-19 vaccine development [38][39][40][41].…”