Safety and immunogenicity of a polyvalent DNA–protein HIV vaccine with matched Env immunogens delivered as a prime–boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial,The Lancet HIV

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Safety and immunogenicity of a polyvalent DNA–protein HIV vaccine with matched Env immunogens delivered as a prime–boost regimen or coadministered in HIV-uninfected adults in the USA (HVTN 124): a phase 1, placebo-controlled, double-blind randomised controlled trial
The Lancet HIV ( IF 12.8 ) Pub Date : 2024-04-29 , DOI: 10.1016/s2352-3018(24)00036-5
Ian Frank ₁ , Shuying S Li ₂ , Nicole Grunenberg ₂ , Edgar T Overton ₃ , Samuel T Robinson ₂ , Hua Zheng ₄ , Kelly E Seaton ₅ , Jack R Heptinstall ₅ , Mary A Allen ₆ , Kenneth H Mayer ₇ , Daniel A Culver ₈ , Michael C Keefer ₉ , Sri Edupuganti ₁₀ , Michael N Pensiero ₆ , Vijay L Mehra ₆ , Stephen C De Rosa ₂ , Daryl E Morris ₂ , Shixia Wang ₁₁ , Michael S Seaman ₁₂ , David C Montefiori ₁₃ , Guido Ferrari ₁₄ , Georgia D Tomaras ₅ , James G Kublin ₂ , Lawrence Corey ₂ , Shan Lu ₁₁ ,

Affiliation

Division of Infectious Disease, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Icon, Burlington, QC, Canada.
Department of Surgery, Duke University, Durham, NC, USA; Department of Immunology, Duke University, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Duke University, Durham, NC, USA; Center for Human Systems Immunology, Duke University, Durham, NC, USA.
Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA; The Fenway Institute, Fenway Health, Boston, MA, USA.
Department of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, GA, USA.
Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Surgery, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
Department of Surgery, Duke University, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA; Duke Human Vaccine Institute, Duke University, Durham, NC, USA; Center for Human Systems Immunology, Duke University, Durham, NC, USA.

An effective HIV vaccine will most likely need to have potent immunogenicity and broad cross-subtype coverage. The aim of the HIV Vaccine Trials Network (HVTN) 124 was to evaluate safety and immunogenicity of a unique polyvalent DNA–protein HIV vaccine with matching envelope (Env) immunogens. HVTN 124 was a randomised, phase 1, placebo-controlled, double-blind study, including participants who were HIV seronegative and aged 18–50 years at low risk for infection. The DNA vaccine comprised five plasmids: four copies expressing Env gp120 (clades A, B, C, and AE) and one p55 (clade C). The protein vaccine included four DNA vaccine-matched GLA-SE-adjuvanted recombinant gp120 proteins. Participants were enrolled across six clinical sites in the USA and were randomly assigned to placebo or one of two vaccine groups (ie, prime–boost or coadministration) in a 5:1 ratio in part A and a 7:1 ratio in part B. Vaccines were delivered via intramuscular needle injection. The primary outcomes were safety and tolerability, assessed via frequency, severity, and attributability of local and systemic reactogenicity and adverse events, laboratory safety measures, and early discontinuations. Part A evaluated safety. Part B evaluated safety and immunogenicity of two regimens: DNA prime (administered at months 0, 1, and 3) with protein boost (months 6 and 8), and DNA–protein coadministration (months 0, 1, 3, 6, and 8). All randomly assigned participants who received at least one dose were included in the safety analysis. The study is registered with ClinicalTrials.gov () and is closed to new participants. Between April 19, 2018 and Feb 13, 2019, 60 participants (12 in part A [five men and seven women] and 48 in part B [21 men and 27 women]) were enrolled. All 60 participants received at least one dose, and 14 did not complete follow-up (six of 21 in the prime–boost group and eight of 21 in the coadminstration group). 11 clinical adverse events deemed by investigators as study-related occurred in seven of 48 participants in part B (eight of 21 in the prime–boost group and three of 21 in the coadministration group). Local reactogenicity in the vaccine groups was common, but the frequency and severity of reactogenicity signs or symptoms did not differ between the prime–boost and coadministration groups (eg, 20 [95%] of 21 in the prime–boost group 21 [100%] of 21 in the coadministration group had either local pain or tenderness of any severity [p=1·00], and seven [33%] nine [43%] had either erythema or induration [p=0·97]), nor did laboratory safety measures. There were no delayed-type hypersensitivity reactions or vasculitis or any severe clinical adverse events related to vaccination. The most frequently reported systemic reactogenicity symptoms in the active vaccine groups were malaise or fatigue (five [50%] of ten in part A and 17 [81%] of 21 in the prime–boost group 15 [71%] of 21 in the coadministration group in part B), headache (five [50%] and 18 [86%] 12 [57%]), and myalgia (four [40%] and 13 [62%] ten [48%]), mostly of mild or moderate severity. Both vaccine regimens were safe, warranting evaluation in larger trials. US National Institutes of Health and US National Institute of Allergy and Infectious Diseases.

更新日期：2024-04-29

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