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
Mina C Hosseinipour, Craig Innes, Sarita Naidoo, Philipp Mann, Julia Hutter, Gita Ramjee, Modulakgotla Sebe, Lucas Maganga, Michael E Herce, Allan C deCamp, Kyle Marshall, One Dintwe, Erica Andersen-Nissen, Georgia D Tomaras, Nonhlanhla Mkhize, Lynn Morris, Ryan Jensen, Maurine D Miner, Giuseppe Pantaleo, Song Ding, Olivier Van Der Meeren, Susan W Barnett, M Juliana McElrath, Lawrence Corey, James G Kublin, HVTN 111 Protocol Team, Nicole Frahm, Barbara Metch, Marguerite Koutsoukos, Stewart Reid, Bupe Sichalwe, Mah Asombang, Christine Namakobo, Sam Mundia, Lumbwe Banda, Joyce Mapanza, Jacinta Shilimi, Emmanuel Kapesa, Abisai Kisinda, Cornelia Lueer, Lilian Njovu, Wiston William, Faith Mlagalila, Elizabeth Ntapara, Willhelmina Olomi, Nnhamo Chiwerengo, Revocatus Kunambi, Bahati Myombe, Rosemary Mwilinga, Neema Mbinda, Joyce Masala, Joseph Mapunda, On Ho, Denelle Reilly, Liz Briesemeister, Marianne Hansen, Jill Zeller, Simba Takuva, Caroline Brackett, Jack Heptinstall, Kelly Seaton, David Beaumont, Lu Zhang, Sheetal Sawant, Marcella Sarzotti-Kelsoe, Tandile Hermanus, Valerie Bekker, Stephen De Rosa, Saleha Omarjee, Stephany Wilcox, Shamiska Rohith, Asiphe Basethi, Renaldo Noble, Daryl Morris, Mina C Hosseinipour, Craig Innes, Sarita Naidoo, Philipp Mann, Julia Hutter, Gita Ramjee, Modulakgotla Sebe, Lucas Maganga, Michael E Herce, Allan C deCamp, Kyle Marshall, One Dintwe, Erica Andersen-Nissen, Georgia D Tomaras, Nonhlanhla Mkhize, Lynn Morris, Ryan Jensen, Maurine D Miner, Giuseppe Pantaleo, Song Ding, Olivier Van Der Meeren, Susan W Barnett, M Juliana McElrath, Lawrence Corey, James G Kublin, HVTN 111 Protocol Team, Nicole Frahm, Barbara Metch, Marguerite Koutsoukos, Stewart Reid, Bupe Sichalwe, Mah Asombang, Christine Namakobo, Sam Mundia, Lumbwe Banda, Joyce Mapanza, Jacinta Shilimi, Emmanuel Kapesa, Abisai Kisinda, Cornelia Lueer, Lilian Njovu, Wiston William, Faith Mlagalila, Elizabeth Ntapara, Willhelmina Olomi, Nnhamo Chiwerengo, Revocatus Kunambi, Bahati Myombe, Rosemary Mwilinga, Neema Mbinda, Joyce Masala, Joseph Mapunda, On Ho, Denelle Reilly, Liz Briesemeister, Marianne Hansen, Jill Zeller, Simba Takuva, Caroline Brackett, Jack Heptinstall, Kelly Seaton, David Beaumont, Lu Zhang, Sheetal Sawant, Marcella Sarzotti-Kelsoe, Tandile Hermanus, Valerie Bekker, Stephen De Rosa, Saleha Omarjee, Stephany Wilcox, Shamiska Rohith, Asiphe Basethi, Renaldo Noble, Daryl Morris
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).
Keywords: Biojector; DNA prime/protein boost; HIV vaccine; subtype C.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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References
- UNAIDS. Global AIDS update. 2018. Available at: . Accessed 18 September 2019.
- Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. . MOPH-TAVEG Investigators Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209–20.
- Russell ND, Marovich MA. Pox-Protein Public Private Partnership program and upcoming HIV vaccine efficacy trials. Curr Opin HIV AIDS 2016; 11:614–9.
- Zambonelli C, Dey AK, Hilt S, et al. . Generation and characterization of a bivalent HIV-1 subtype C gp120 protein boost for proof-of-concept HIV vaccine efficacy trials in Southern Africa. PLoS One 2016; 11:e0157391.
- Bekker LG, Moodie Z, Grunenberg N, et al. . HVTN 100 Protocol Team Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial. Lancet HIV 2018; 5:e366–78.
- Spearman P, Lally MA, Elizaga M, et al. . HIV Vaccine Trials Network of NIAID A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis 2011; 203:1165–73.
- Li J, Valentin A, Kulkarni V, et al. . HIV/SIV DNA vaccine combined with protein in a co-immunization protocol elicits highest humoral responses to envelope in mice and macaques. Vaccine 2013; 31:3747–55.
- Patel V, Jalah R, Kulkarni V, et al. . DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge. Proc Natl Acad Sci U S A 2013; 110:2975–80.
- Graham BS, Enama ME, Nason MC, et al. . VRC 008 Study Team DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial. PLoS One 2013; 8:e59340.
- Graham BS, Martin JE, Gordon IJ, et al. . Evaluation of candidate DNA HIV-1 vaccine delivery by Biojector or needle and syringe in health adults (VRC 008). In: AIDS vaccine. Seattle, WA:2007.
- Pantaleo G, Janes H, Karuna S, et al. . NIAID HIV Vaccine Trials Network Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial. Lancet HIV 2019; 6:e737–49.
- Haynes BF, Gilbert PB, McElrath MJ, et al. . Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 2012; 366:1275–86.
- Yates NL, deCamp AC, Korber BT, et al. . HIV-1 envelope glycoproteins from diverse clades differentiate antibody responses and durability among vaccinees. J Virol 2018; 92 pii: e01843–17.
- Yates NL, Liao HX, Fong Y, et al. . Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med 2014; 6:228ra39.
- Zolla-Pazner S, deCamp A, Gilbert PB, et al. . Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLoS One 2014; 9:e87572.
- Sarzotti-Kelsoe M, Bailer RT, Turk E, et al. . Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. J Immunol Methods 2014; 409:131–46.
- Bull M, Lee D, Stucky J, et al. . Defining blood processing parameters for optimal detection of cryopreserved antigen-specific responses for HIV vaccine trials. J Immunol Methods 2007; 322:57–69.
- De Rosa SC, Carter DK, McElrath MJ. OMIP-014: validated multifunctional characterization of antigen-specific human T cells by intracellular cytokine staining. Cytometry A 2012; 81:1019–21.
- Horton H, Thomas EP, Stucky JA, et al. . Optimization and validation of an 8-color intracellular cytokine staining (ICS) assay to quantify antigen-specific T cells induced by vaccination. J Immunol Methods 2007; 323:39–54.
- Wilcoxon F. Individual comparisons of grouped data by ranking methods. J Econ Entomol 1946; 39:269.
- Agresti A, Coull BA. Approximate is better than “exact” for interval estimation of binomial proportions. Am Stat 1998; 52:119–26.
- Lin L, Finak G, Ushey K, et al. . COMPASS identifies T-cell subsets correlated with clinical outcomes. Nat Biotechnol 2015; 33:610–6.
Source: PubMed