EHVA P01/ANRS VRI08: A Prophylactic HIV Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DREP Alone and in Combination With a Clade C ENV Protein in Healthy HIV-uninfected Adults

EHVA P01 is an international, phase I, prophylactic HIV vaccine trial to evaluate the safety and immunogenicity of HIV Clade C DREP alone and in Combination with a Clade C ENV protein in healthy HIV-uninfected adults.

开始日期2022-08-05

申办/合作机构

ANRS, Emerging Infectious Diseases

[+6]

NCT04066881

/ Completed临床2期IIT

A Phase IIb Three-arm, Two-stage HIV Prophylactic Vaccine Trial With a Second Randomisation to Compare TAF/FTC to TDF/FTC as Pre-exposure Prophylaxis

This international, multi-centre, double-blind vaccine study is a three-arm prospective 1:1:1 randomisation comparing each of two experimental combination vaccine regimens i.e. DNA/AIDSVAX (weeks 0,4,24,48) and DNA/CN54gp140 (weeks 0,4) + MVA/CN54gp140 (weeks 24,48) with placebo control. There will be a concurrent open-label 1:1 randomisation to compare daily TAF/FTC (week 0-26) to daily TDF/FTC (weeks 0-26) as pre-exposure prophylaxis.
The study aims to randomise up to 1668 eligible adults (18-40 years) through collaborating clinical research centres in 4 countries (Mozambique; South Africa; Tanzania; and Uganda). Each participant will be followed for a minimum of 74 weeks after enrolment.
The trial is designed to detect a reduction in HIV incidence that has public health relevance sufficient to justify implementation of the combination vaccine regimen. In light of the high level of effectiveness demonstrated in the PrEP trials (up to 86% reduction in HIV), this trial is powered to detect a protective vaccine efficacy of 70% at the final analysis.
The PrEP component will determine whether the effectiveness of TAF/FTC is unacceptably lower than the effectiveness of TDF/FTC.

开始日期2020-12-15

申办/合作机构

International AIDS Vaccine Initiative, Inc.

[+10]

NCT02915016

/ Completed临床1/2期IIT

A Phase 1/2a Clinical Trial to Evaluate the Safety and Immunogenicity of HIV Clade C DNA, and of MF59®- or AS01B-Adjuvanted Clade C Env Protein in Various Combinations, in Healthy, HIV-Uninfected Adult Participants

This study will evaluate the safety and immune response to the DNA-HIV-PT123 vaccine used in combination with one of two protein vaccines (Bivalent Subtype C gp120/MF59 or Bivalent Subtype C gp120/AS01B) in healthy, HIV-uninfected adults.

开始日期2016-12-07

申办/合作机构

National Institute of Allergy & Infectious Diseases

100 项与 DNA-HIV-PT123 vaccine(National Institute of Allergy & Infectious Diseases) 相关的临床结果

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项与 DNA-HIV-PT123 vaccine(National Institute of Allergy & Infectious Diseases) 相关的文献（医药）

2024-11-01·eClinicalMedicine

Safety and immunogenicity of CD40.HIVRI.Env, a dendritic cell-based HIV vaccine, in healthy HIV-uninfected adults: a first-in-human randomized, placebo-controlled, dose-escalation study (ANRS VRI06)

Article

作者: Centlivre, Mireille ; Wiedemann, Aurélie ; Thiebaut, Rodolphe ; Levy, Yves ; Diallo, Alpha ; Launay, Odile ; Lelièvre, Jean-Daniel ; Hardel, Lucile ; Tomaras, Georgia D ; Lacabaratz, Christine ; Rieux, Véronique ; Zurawski, Sandra ; Zurawski, Gerard ; Pantaleo, Giuseppe ; Candotti, Fabio ; Cardinaud, Sylvain ; Durand, Mélany ; Ding, Song ; Moog, Christiane ; Richert, Laura

BackgroundCurrent HIV prophylactic vaccines evaluate HIV Env as purified proteins. CD40.HIVRI.Env is an innovative antigen delivery targeting gp140 Env from HIV Clade C 96ZM651 to CD40-expressing antigen-presenting cells, thus harnessing the intrinsic immune-stimulant properties. DNA-HIV-PT123 vaccine encodes 96ZM651 gp140/Gag and 97CN54 Pol/Nef.MethodsSeventy-two HIV-negative volunteers were enrolled between 05/2021 and 10/2022 in a phase 1 placebo-controlled trial conducted in France and Switzerland (N° EudraCT: 2020-001814-40; NCT04842682). Volunteers were randomized (5:1 active versus placebo) in groups receiving either 0.3, 1.0, or 3.0 mg CD40.HIVRI.Env (Hiltonol® adjuvanted) alone or co-administered with DNA-HIV-PT123 at weeks (W) 0, 4, and 24. Safety and immunogenicity were monitored until W48. The primary safety endpoint was the proportion of participants per dose cohort and randomized arm without any grade 3 or 4 biological (abnormal laboratory values), or clinical local or systemic solicited, or unsolicited adverse events between W0 and W48 considered to be related or possibly related to the investigational products.FindingsCD40.HIVRI.Env was well tolerated. Env-specific CD4⁺ T-cells (IL-2⁺ or IFN-γ⁺ or TNF⁺) were detected in all vaccinees from W6 to W26 and persisted until W48 without a dose-response signal or an effect of DNA-HIV-PT123 co-administration. At W26, IgG response rates (RR) against autologous and nine heterologous gp120/gp140 were 89-100% across all groups and 56-100% at W48. RR against 96ZM651gp70V1V2 were high (90-100%) at W6 and W26 in all groups. Tier1A MW965.26 neutralizing antibody (nAb) titres were detectable in 50-100% of vaccinated individuals at W26, with a dose-response signal, while one volunteer developed nAbs against five Tier2 viruses.InterpretationCD40.HIVRI.Env alone or administered with DNA-HIV-PT123 was safe and induced early, and sustained anti-Env cellular and V1V2 IgG responses, identified as correlates of protection in the RV144 trial. CD40 targeting Env-based vaccines may be instrumental for inducing protective vaccine responses in prime-boost strategies.FundingANRS Emerging infectious diseases (ANRS MIE); Vaccine Research Institute (VRI).

2024-08-01·JAIDS Journal of Acquired Immune Deficiency Syndromes

Safety and Immunogenicity of a DNA Vaccine With Subtype C gp120 Protein Adjuvanted With MF59 or AS01B: A Phase 1/2a HIV-1 Vaccine Trial

Article

作者: Grunenberg, Nicole ; Jones, Megan ; Jensen, Ryan L. ; Ferrari, Guido ; Gray, Glenda E ; Dintwe, One ; Hosseinipour, Mina C ; Van Der Meeren, Olivier ; Robinson, Samuel T ; Kublin, James G. ; Tomaras, Georgia D ; Monaco, Cynthia L. ; Kublin, James G ; Koutsoukos, Marguerite ; Andersen-Nissen, Erica ; Jensen, Ryan L ; Seaton, Kelly E. ; Huang, Yunda ; Gilbert, Peter B. ; Hosseinipour, Mina C. ; Mann, Philipp ; deCamp, Allan ; McElrath, M Juliana ; Monaco, Cynthia L ; Lu, Huiyin ; Church, E Chandler ; Heptinstall, Jack ; Tomaras, Georgia D. ; Church, E. Chandler ; Ding, Song ; McElrath, M. Juliana ; Gilbert, Peter B ; Hutter, Julia ; Garrett, Nigel ; Gray, Glenda E. ; Seaton, Kelly E ; Robinson, Samuel T. ; Corey, Lawrence ; Pantaleo, Giuseppe

Background:An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B.Methods:HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination.Results:From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose.Conclusions:The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016.

2019-09-30·Journal of Clinical Investigation1区 · 医学

DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial

1区 · 医学

Article

作者: Rouphael, Nadine G ; Jensen, Ryan ; Li, Shuying S ; Wilson, Gregory J ; Montefiori, David C ; Pantaleo, Giuseppe ; Norwood, Aliza ; Sinangil, Faruk ; De Rosa, Stephen C ; Morgan, Cecilia ; Karuna, Shelly ; Sanchez, Brittany ; Ferrari, Guido ; Swann, Edith ; Maenza, Janine ; Tomaras, Georgia D ; Tieu, Hong-Van ; Sobieszczyk, Magdalena E ; Kobie, James ; Keefer, Michael C ; Frank, Ian ; McElrath, M Juliana ; Ding, Song

BACKGROUNDRV144 is the only preventive HIV vaccine regimen demonstrating efficacy in humans. Attempting to build upon RV144 immune responses, we conducted a phase 1, multicenter, randomized, double-blind trial to assess the safety and immunogenicity of regimens substituting the DNA-HIV-PT123 (DNA) vaccine for ALVAC-HIV in different sequences or combinations with AIDSVAX B/E (protein).METHODSOne hundred and four HIV-uninfected participants were randomized to 4 treatment groups (T1, T2, T3, and T4) and received intramuscular injections at 0, 1, 3, and 6 months (M): T1 received protein at M0 and M1 and DNA at M3 and M6; T2 received DNA at M0 and M1 and protein at M3 and M6; T3 received DNA at M0, M1, M3, and M6 with protein coadministered at M3 and M6; and T4 received protein and DNA coadministered at each vaccination visit.RESULTSAll regimens were well tolerated. Antibodies binding to gp120 and V1V2 scaffold were observed in 95%-100% of participants in T3 and T4, two weeks after final vaccination at high magnitude. While IgG3 responses were highest in T3, a lower IgA/IgG ratio was observed in T4. Binding antibodies persisted at 12 months in 35%-100% of participants. Antibody-dependent cell-mediated cytotoxicity and tier 1 neutralizing-antibody responses had higher response rates for T3 and T4, respectively. CD4+ T cell responses were detectable in all treatment groups (32%-64%) without appreciable CD8+ T cell responses.CONCLUSIONThe DNA/protein combination regimens induced high-magnitude and long-lasting HIV V1V2-binding antibody responses, and early coadministration of the 2 vaccines led to a more rapid induction of these potentially protective responses.TRIAL REGISTRATIONClinicalTrials.gov NCT02207920.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID) grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069511, UM1 AI069470, UM1 AI069534, P30 AI450008, UM1 AI069439, UM1 AI069481, and UM1 AI069496; the National Center for Advancing Translational Sciences, NIH (grant UL1TR001873); and the Bill & Melinda Gates Foundation (grant OPP52845).

100 项与 DNA-HIV-PT123 vaccine(National Institute of Allergy & Infectious Diseases) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
获得性免疫缺陷综合征	临床3期	乌干达	EuroVacc Foundation	2014-09-01
曼氏血吸虫病	临床3期	乌干达	EuroVacc Foundation	2014-09-01
HIV感染	临床2期	-	National Institute of Allergy & Infectious Diseases	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02915016 (HVTN108, CTgov)	临床1/2期	HIV感染	334	Placebo+DNA-HIV-PT123 vaccine+Bivalent Subtype C gp120/MF59 vaccine (Group 1: DNA-HIV-PT123 + Placebo + Protein/MF59)	糧繭製遞廠鹽蓋鬱壓夢(膚糧憲膚積憲襯窪餘鑰) = 衊壓餘壓鏇網壓願遞醖齋淵簾範顧窪窪淵壓願 (積廠衊鹹觸醖壓壓鏇夢, 窪衊鏇觸蓋網夢淵襯膚 ~ 構鑰築鑰構糧餘鹹齋遞) 更多	-	2020-09-16
				Placebo+Bivalent Subtype C gp120/AS01B vaccine+DNA-HIV-PT123 vaccine (Group 2: DNA-HIV-PT123 + Placebo + Protein/AS01B)	糧繭製遞廠鹽蓋鬱壓夢(膚糧憲膚積憲襯窪餘鑰) = 糧齋醖壓獵範鹹選鹹醖齋淵簾範顧窪窪淵壓願 (積廠衊鹹觸醖壓壓鏇夢, 觸築範鑰糧製壓顧襯醖 ~ 襯憲窪遞遞積選製遞膚) 更多