Browsing by Author "Dintwe O"

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    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.
    (2021-Jan-23) Hosseinipour MC; Innes C; Naidoo S; Mann P; Hutter J; Ramjee G; Sebe M; Maganga L; Herce ME; deCamp AC; Marshall K; Dintwe O; Andersen-Nissen E; Tomaras GD; Mkhize N; Morris L; Jensen R; Miner MD; Pantaleo G; Ding S; Van Der Meeren O; Barnett SW; McElrath MJ; Corey L; Kublin JG; National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.; NIMR-Mbeya Medical Research Center, Mbeya, Tanzania.; Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; Aurum Institute, Klerksdorp, South Africa.; GSK Vaccines, Rixensart, Belgium.; Cape Town HVTN Immunology Laboratory, Cape Town, South Africa.; EuroVacc Foundation, Lausanne, Switzerland.; UNC Project-Malawi, Lilongwe, Malawi.; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Aurum Institute, Tembisa, South Africa.; HIV Prevention Research Unit, South African Medical Research Council, Durban, South Africa.; GSK Vaccines, Cambridge, Massachusetts, USA.; Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.; Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    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).
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    Protein Dose-Sparing Effect of AS01B Adjuvant in a Randomized Preventive HIV Vaccine Trial of ALVAC-HIV (vCP2438) and Adjuvanted Bivalent Subtype C gp120.
    (2024-Aug-16) Chirenje ZM; Laher F; Dintwe O; Muyoyeta M; deCamp AC; He Z; Grunenberg N; Laher Omar F; Seaton KE; Polakowski L; Woodward Davis AS; Maganga L; Baden LR; Mayer K; Kalams S; Keefer M; Edupuganti S; Rodriguez B; Frank I; Scott H; Stranix-Chibanda L; Gurunathan S; Koutsoukos M; Van Der Meeren O; DiazGranados CA; Paez C; Andersen-Nissen E; Kublin J; Corey L; Ferrari G; Tomaras G; McElrath MJ; Department of Medicine, University of Rochester, Rochester, NewYork, USA.; SanFrancisco Department of Public Health, San Francisco, California, USA.; Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.; Faculty of Medicine and Health Science, University of Zimbabwe Clinical Trials Research Centre, University of Zimbabwe, Harare, Zimbabwe.; National Institute for Medical Research-Mbeya Medical Research Centre, Mbeya, Tanzania.; Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts, USA.; Cape Town HIV Vaccine Trials Network Immunology Laboratory, Cape Town, South Africa.; Department of Obstetrics and Gynecology, University of California San Francisco, San Francisco, California, USA.; Department of Medicine, Emory University, Atlanta, Georgia, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.; School of Medicine, University of Pennsylvania, Philadelphia, USA.; GSK, Wavre, Belgium.; GSK, Rixensart, Belgium.; Center for Human Systems Immunology, Duke University School of Medicine, Durham, North Carolina, USA.; Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University/University Hospitals, Cleveland Medical Center, Cleveland, Ohio, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.; The Fenway Institute, Fenway Health, Boston, Massachusetts, USA.; Centre for Infectious Diseases Research in Zambia, Livingstone, Zambia.; Sanofi Pasteur, Swiftwater, Pennsylvania, USA.; CIDRZ; Centre for Infectious Disease Research in Zambia (CIDRZ)
    BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled human immunodeficiency virus (HIV) vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at 2 dose levels in healthy HIV-uninfected adults. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200 μg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40 μg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% women, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40 μg gp120/AS01B group were higher than in either of the 200 μg gp120 groups. CONCLUSIONS: The 40 μg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses. Clinical Trials Registration . NCT03122223.