HIV Vaccine Studies

HIV疫苗研究

• 批准号: 10497733
• 负责人: Julie E. Ledgerwood
• 金额: $ 630.05万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10497733
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Adenovirus Vector; Adenoviruses; Adult; Antibody titer measurement; Biological Assay; Clinical Research; Clinical Trials; Collaborations; DNA; DNA Vaccines; Data Analyses; Development; Devices; Dose; Enrollment; Epidemic; Evaluation; Follow-Up Studies; Futility; HIV; HIV Infections; HIV Vaccine Trials Network; HIV vaccine; HIV-1; HIV-1 vaccine; Immune; Immunize; Injections; Intramuscular; Investigation; Kinetics; Longterm Follow-up; Methods; Needles; Participant; Pattern; Phase; Phase I Clinical Trials; Placebos; Plasmids; Polyproteins; Preventive; Preventive vaccine; Public Health; Publishing; Randomized; Recombinants; Recommendation; Regimen; Research Personnel; Route; Safety; Schedule; Secondary Immunization; Serotyping; Site; Syringes; Therapeutic Studies; Vaccination; Vaccine Research; Vaccines; Viral Load result; adaptive immune response; aluminum sulfate; base; clinical center; design; dosage; efficacy study; env Glycoproteins; follow-up; gag Gene Products; i(19); immunogenicity; nef Protein; novel; novel strategies; open label; phase 1 study; plasmid DNA; pol Gene Products; programs; prospective; prototype; research study; subcutaneous; therapeutic vaccine; vaccine candidate; vaccine evaluation; vaccine trial; vector vaccine

This Vaccine Research Center (VRC) Clinical Trials Program (CTP) project is for clinical research related to preventive and therapeutic vaccines directed against HIV. Preventive HIV-1 vaccine candidates have included: DNA vaccine constructs, a recombinant adenoviral vector serotype 5(rAd5) vaccine, a recombinant adenoviral vector serotype 35 (rAd35) vaccine, and a trimer based vaccine with alum. Therapeutic vaccine candidates have included: DNA vaccine constructs and a recombinant adenoviral vector vaccine. Studies have been designed to evaluate dose, immunogenicity, route and device of administration, and prime-boost regimens. VRC 001 (01-I-0079) evaluated a clade B, single plasmid DNA vaccine developed by the VRC in collaboration with other intramural investigators. Published: J Acquir Immune Defic Syndr, 2007. 44(5):p.601-5. VRC 004 (03-I-0022) was the first Phase I clinical trial of a multiclade 4-plasmid DNA vaccine, VRC-HIVDNA009-00-VP, which expresses a Gag-Pol-Nef polyprotein from clade B HIV-1 and Env glycoproteins from clades A, B and C. This study evaluated the 2 mg, 4 mg and 8 mg dosage. Results published: J Infect Dis, 2006. 194(12):p.1650-60. Long-term follow-up was completed in FY08. VRC 006 (04-I-0128) was the first Phase I clinical trial of an investigational recombinant serotype 5 adenoviral vector (rAd5) vaccine, VRC-HIVADV014-00-VP, for the prevention of HIV infection. This vaccine is composed of 4 adenoviral vectors (in a 3:1:1:1 ratio) that encode for the HIV-1 Gag/Pol polyprotein from clade B and HIV-1 Env glycoproteins from clades A, B, and C, respectively. This study evaluated three dosages. Results published: J Infect Dis, 2006. 194(12):p.1638-49. Long-term follow-up was completed in FY09. VRC 007 (04-I-0254) was the first Phase I clinical trial of a multiclade 6-plasmid HIV-1 DNA vaccine, VRC-HIVDNA016-00-VP, which expresses Gag, Pol and Nef proteins from clade B HIV-1 and Env glycoproteins from clades A, B and C. The 4 mg dosage was evaluated. Published: Vaccine, 2007. 25(20):p.4085-92. VRC 008 (05-I-0148) was a Phase I study of the prime-boost vaccination regimen consisting of 3 vaccinations with the 6-plasmid DNA vaccine followed by a boost with the rAd5 vaccine. This study evaluated the safety and immunogenicity of both Biojector and needle/syringe as injection devices for the DNA vaccine, as well as safety and immunogenicity of two different dosages for the rAd5 booster. The study was designed to enroll equal numbers of subjects with low and high antibody titers to adenovirus serotype 5. During FY08 week 94 long-term follow-up evaluations and analysis of the primary immunogenicity assays was completed. Published: PLoS One, 2013; 8(4):e59340. VRC 009 (05-I-0081) was a Phase I study of the rAd5 vaccine as a booster vaccination in subjects previously immunized with the 4 mg or 8 mg dose of the 4-plasmid multiclade DNA vaccine in the VRC 004 study. Ten subjects enrolled. Similarly, VRC 010 (05-I-0140) was a Phase I study of the rAd5 vaccine as a booster vaccination in subjects previously immunized with 4 mg of the 6-plasmid multiclade DNA vaccine in the VRC 007 study. Only a small number of subjects were eligible to participate; 4 subjects enrolled and completed the 24 weeks of follow-up. Published: PLoS One, Feb 2010, 5(2):p.1-15 VRC 101 (06-I-0056) was the first Phase I therapeutic study of two candidate HIV-1 vaccines developed by the VRC and administered in a prime-boost regimen. Published: J Infect Dis. 2013 Jun 15;207(12):1829-40. VRC 011 (06-I-0149) was a Phase I study to evaluate the intramuscular, subcutaneous and intradermal routes of administration for priming vaccinations with either 3 injections of the 6-plasmid DNA vaccine or one injection of the rAd5 vaccine. In all schedules a rAd5 booster injection was administered IM. Sixty subjects were enrolled; equal numbers of subjects had negative and positive antibody titers to adenovirus serotype 5 at enrollment. Follow-up of study participants was completed in FY 09. Published: PLoS One, 2014 Mar 12;9(3). VRC 012 (07-I-0167) was a Phase I study to evaluate a novel prototype adenoviral vector serotype 35 vaccine (rAd 35-EnvA) at three dosages in Part I of the study and then in Part II of the study heterologous prime-boost schedules with an rAd5-EnvA vaccine will be evaluated. During FY08, Part I enrollments and vaccinations were completed. The enrollments and study vaccinations for Part II of the study were completed in FY10. Published: PLoS One. 2016 Nov 15;11(11). VRC 015 (08-I-0171) was a Phase I study to evaluate the safety and immunogenicity of both Biojector and needle/syringe as injection devices for the recombinant serotype 5 adenoviral vector (rAd5) vaccine, VRC-HIVADV014-00-VP. Enrollments and study vaccinations were completed in FY10; long-term follow-up was completed in FY14. Published: PLoS One. 2014 Sep 29;9(9). VRC 016 (11-I-0197) was a Phase Ib descriptive study to evaluate the kinetics and pattern of early innate and adaptive immune responses to the rAd5 vaccine, VRC-HIVADV014-00-VP, alone and after priming with a DNA vaccine. This study was initiated in FY11 and follow-up completed in FY14. HVTN 505 (09-I-0163) was a multicenter Phase 2b efficacy study of the VRC candidate DNA prime-rAd5 boost HIV vaccine regimen for which the VRC Clinical Trials Core is participating as a site. After Phase 1/2 safety and immunogenicity evaluations of the vaccines were completed, this study was developed in collaboration with the Division of AIDS and HVTN and designed to see whether or not the vaccines have efficacy in prevention of HIV or an effect on HIV viral load in vaccine recipients as compared to placebo recipients who acquire HIV infection during 2 years of follow-up. Study enrollments were completed in FY13. Study vaccinations were discontinued in April 2013 based on DSMB recommendations when study results showed that prospectively defined efficacy futility criteria had been met. Long term follow-up is ongoing. Published: N Engl J Med. 2013 Nov 28;369(22):2083-92. VRC 018 (19-I-0031) is a phase 1 dose escalation, randomized, open-label clinical trial to evaluate dose, safety, tolerability and immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, with alum in healthy adults. The trial was initiated in FY19 and enrollment completed in FY 20. Data analysis is ongoing.

该疫苗研究中心 (VRC) 临床试验计划 (CTP) 项目旨在进行与针对 HIV 的预防性和治疗性疫苗相关的临床研究。预防性 HIV-1 候选疫苗包括：DNA 疫苗构建体、重组腺病毒载体血清型 5 (rAd5) 疫苗、重组腺病毒载体血清型 35 (rAd35) 疫苗和基于三聚体的明矾疫苗。候选治疗性疫苗包括：DNA 疫苗构建体和重组腺病毒载体疫苗。研究旨在评估剂量、免疫原性、给药途径和装置以及初免-加强方案。 VRC 001 (01-I-0079) 评估了 VRC 与其他校内研究人员合作开发的进化枝 B、单质粒 DNA 疫苗。出版：J Acquir Immune Defic Syndr，2007。44(5)：p.601-5。 VRC 004 (03-I-0022) 是多进化枝 4 质粒 DNA 疫苗 VRC-HIVDNA009-00-VP 的第一个 I 期临床试验，该疫苗表达来自进化枝 B HIV-1 的 Gag-Pol-Nef 多蛋白和来自进化枝 A、B 和 C 的 Env 糖蛋白。这项研究评估了 2 mg、4 mg 和 8 mg 剂量。结果发表：J Infect Dis，2006。194(12)：p.1650-60。长期随访于 2008 财年完成。 VRC 006 (04-I-0128) 是研究性重组血清型 5 腺病毒载体 (rAd5) 疫苗 VRC-HIVADV014-00-VP 的第一个 I 期临床试验，用于预防 HIV 感染。该疫苗由 4 个腺病毒载体（比例为 3:1:1:1）组成，分别编码来自进化枝 B 的 HIV-1 Gag/Pol 多蛋白和来自进化枝 A、B 和 C 的 HIV-1 Env 糖蛋白。这项研究评估了三种剂量。结果发表：J Infect Dis，2006。194(12)：p.1638-49。长期随访于 2009 财年完成。 VRC 007 (04-I-0254) 是多进化枝 6 质粒 HIV-1 DNA 疫苗 VRC-HIVDNA016-00-VP 的第一个 I 期临床试验，该疫苗表达来自进化枝 B HIV-1 的 Gag、Pol 和 Nef 蛋白以及来自进化枝 A、B 和 C 的 Env 糖蛋白。评估了 4 mg 剂量。出版：疫苗，2007 年。25(20)：p.4085-92。 VRC 008 (05-I-0148) 是初免-加强疫苗接种方案的 I 期研究，包括使用 6 质粒 DNA 疫苗进行 3 次疫苗接种，然后使用 rAd5 疫苗加强接种。本研究评估了 Biojector 和针头/注射器作为 DNA 疫苗注射装置的安全性和免疫原性，以及 rAd5 加强剂的两种不同剂量的安全性和免疫原性。该研究旨在招募相同数量的腺病毒血清型 5 低抗体滴度和高抗体滴度受试者。在 2008 财年第 94 周，完成了主要免疫原性测定的 94 次长期随访评估和分析。出版：《公共科学图书馆一号》，2013 年； 8（4）：e59340。 VRC 009 (05-I-0081) 是 rAd5 疫苗的 I 期研究，作为 VRC 004 研究中先前接种过 4 mg 或 8 mg 剂量的 4 质粒多进化枝 DNA 疫苗的受试者的加强疫苗接种。报名了十个科目。同样，VRC 010 (05-I-0140) 是一项 rAd5 疫苗的 I 期研究，作为先前在 VRC 007 研究中接种过 4 毫克 6 质粒多进化枝 DNA 疫苗的受试者的加强疫苗接种。只有少数受试者有资格参加； 4 名受试者入组并完成了 24 周的随访。出版： PLoS One，2010 年 2 月，5(2)：p.1-15 VRC 101 (06-I-0056) 是 VRC 开发的两种候选 HIV-1 疫苗的第一个 I 期治疗研究，并以初免-加强方案进行施用。出版：J Infect Dis。 2013 年 6 月 15 日；207(12)：1829-40。 VRC 011 (06-I-0149) 是一项 I 期研究，旨在评估 3 次 6-质粒 DNA 疫苗注射或 1 次 rAd5 疫苗注射引发疫苗的肌内、皮下和皮内给药途径。在所有时间表中，rAd5加强注射均通过肌内注射进行。注册了 60 名受试者；在入组时，相同数量的受试者对腺病毒血清型 5 的抗体滴度呈阴性和阳性。研究参与者的随访于 2009 财年完成。发表：PLoS One，2014 年 3 月 12 日；9(3)。 VRC 012 (07-I-0167) 是一项 I 期研究，旨在评估新型腺病毒载体血清型 35 疫苗 (rAd 35-EnvA) 的三个剂量，在研究的第一部分中，然后在研究的第二部分中，将评估 rAd5-EnvA 疫苗的异源初免-加强方案。 2008 财年期间，第一部分的登记和疫苗接种工作已完成。该研究第二部分的入组和研究疫苗接种已于 2010 财年完成。出版：公共科学图书馆一号。 2016年11月15日；11(11)。 VRC 015 (08-I-0171) 是一项 I 期研究，旨在评估 Biojector 和针头/注射器作为重组血清型 5 腺病毒载体 (rAd5) 疫苗 VRC-HIVADV014-00-VP 注射装置的安全性和免疫原性。 2010 财年完成了登记和研究疫苗接种；长期随访于 2014 财年完成。出版：公共科学图书馆一号。 2014 年 9 月 29 日；9(9)。 VRC 016 (11-I-0197) 是一项 Ib 期描述性研究，旨在评估单独使用 rAd5 疫苗 VRC-HIVADV014-00-VP 和使用 DNA 疫苗引发后的早期先天性和适应性免疫反应的动力学和模式。这项研究于 2011 财年启动，后续行动于 2014 财年完成。 HVTN 505 (09-I-0163) 是 VRC 候选 DNA prime-rAd5 增强 HIV 疫苗方案的多中心 2b 期疗效研究，VRC 临床试验核心作为站点参与其中。在疫苗的 1/2 期安全性和免疫原性评估完成后，这项研究是与艾滋病司和 HVTN 合作开展的，旨在观察与在 2 年随访期间感染 HIV 的安慰剂接受者相比，疫苗是否能有效预防 HIV 或对疫苗接受者的 HIV 病毒载量产生影响。研究注册于 2013 财年完成。根据 DSMB 的建议，研究疫苗接种于 2013 年 4 月停止，当时研究结果显示满足了前瞻性定义的有效性无效标准。长期随访正在进行中。出版：N Engl J Med。 2013 年 11 月 28 日；369(22):2083-92。 VRC 018 (19-I-0031) 是一项 1 期剂量递增、随机、开放标签临床试验，旨在评估健康成人中使用明矾的 HIV-1 疫苗 VRC-HIVRGP096-00-VP 的剂量、安全性、耐受性和免疫原性。 该试验于 2019 财年启动，入组于 20 财年完成。数据分析正在进行中。