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
Authors: Hosseinipour Mina C , Innes Craig , Naidoo Sarita , Mann Philipp , Hutter Julia , Ramjee Gita , Sebe Modulakgotla , Maganga Lucas , Herce Michael E , deCamp Allan C , Marshall Kyle , Dintwe One , Andersen-Nissen Erica , Tomaras Georgia D , Mkhize Nonhlanhla , Morris Lynn , Jensen Ryan , Miner Maurine D , Pantaleo Giuseppe , Ding Song , Van Der Meeren Olivier , Barnett Susan W , McElrath M Juliana , Corey Lawrence , Kublin James G ,   HVTN 111 Protocol Team, Frahm Nicole , Metch Barbara , Koutsoukos Marguerite , Reid Stewart , Sichalwe Bupe , Asombang Mah , Namakobo Christine , Mundia Sam , Banda Lumbwe , Mapanza Joyce , Shilimi Jacinta , Kapesa Emmanuel , Kisinda Abisai , Lueer Cornelia , Njovu Lilian , William Wiston , Mlagalila Faith , Ntapara Elizabeth , Olomi Willhelmina , Chiwerengo Nnhamo , Kunambi Revocatus , Myombe Bahati , Mwilinga Rosemary , Mbinda Neema , Masala Joyce , Mapunda Joseph , Ho On , Reilly Denelle , Briesemeister Liz , Hansen Marianne , Zeller Jill , Takuva Simba , Brackett Caroline , Heptinstall Jack , Seaton Kelly , Beaumont David , Zhang Lu , Sawant Sheetal , Sarzotti-Kelsoe Marcella , Hermanus Tandile , Bekker Valerie , De Rosa Stephen , Omarjee Saleha , Wilcox Stephany , Rohith Shamiska , Basethi Asiphe , Noble Renaldo , Morris Daryl 
Published: January 2020

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).