HIV Preventive Vaccine Studies

HIV预防疫苗研究

• 批准号: 7964840
• 负责人: Barney Graham
• 金额: $ 178.57万
• 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/7964840
• 关键词: Adenovirus Vector; Adenoviruses; Affect; Antibodies; Biological Assay; Clinic; Clinical; Clinical Research; Clinical Trials; Clinical trial protocol document; Collaborations; DNA; DNA Vaccines; Devices; Dose; Educational Materials; Eligibility Determination; Enrollment; Epidemic; Evaluation; Follow-Up Studies; Gagging; HIV; HIV Infections; HIV Vaccine Trials Network; HIV vaccine; HIV-1; HIV-1 vaccine; Immune; Infection; Injection of therapeutic agent; Intramuscular; Manuscripts; Needles; Participant; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Placebos; Plasmids; Polyproteins; Prevention; Preventive; Protocols documentation; Public Health; Publishing; Recombinants; Research Personnel; Research Project Grants; Route; Safety; Schedule; Screening procedure; Secondary Immunization; Serotyping; Site; Syringes; Treatment Protocols; United States National Institutes of Health; Vaccination; Vaccine Clinical Trial; Vaccines; Viral Load result; design; dosage; env Glycoproteins; follow-up; immunogenicity; nef Protein; novel; novel strategies; plasmid DNA; pol Gene Products; prevent; programs; prototype; subcutaneous; vaccine evaluation

Summary: This clinical research project is for clinical trials related to preventive HIV vaccines conducted at the VRC Clinic at the NIH Clinical Center. These consist of a screening protocol and clinical trials to evaluate candidate preventive HIV-1 vaccines including: DNA vaccine constructs, a recombinant adenoviral vector serotype 5(rAd5) vaccine, and a recombinant adenoviral vector serotype 35 (rAd35) vaccine. Studies have been designed to evaluate dose, immunogenicity, route of administration, device for administration and prime-boost regimens. A brief summary of each study to date follows. The screening protocol, VRC 000 (02-I-0127), facilitates recruitment and screening of healthy, HIV-negative subjects for investigational preventive HIV vaccine clinical trials. Educational materials on vaccines are reviewed with and provided to subjects before enrollment into a study. Prior to the establishment of the VRC Clinic, a Phase I study VRC 001 (01-I-0079) of a clade B, single plasmid DNA vaccine developed by VRC was conducted through collaboration with other intramural investigators. A manuscript describing results wss published in FY07 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. In FY07 a manuscript describing results was published J Infect Dis, 2006. 194(12): p. 1650-60. The long-term follow-up for the protocol was completed during 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. In FY07 a manuscript describing results was published J Infect Dis, 2006. 194(12): p. 1638-49. The long-term follow-up for the protocol was completed during 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. In FY07 a manuscript describing study results was published Vaccine, 2007. 25(20): p. 4085-92. VRC 008 (05-I-0148) is 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 at enrollment in order to gain a better understanding of whether pre-existing antibody affects the safety and immunogenicity of the rAd5 booster. During FY08 week 94 long-term follow-up evaluations were completed and analysis of the primary immunogenicity assays were completed. VRC 009 (05-I-0081) is 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. During FY07 statistical analysis of the study was completed and a manuscript of study results from VRC 009 and 010 combined is under review. VRC 010 (05-I-0140) is 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. During FY07 statistical analysis of the study was completed and a manuscript of study results from VRC 009 and 010 combined is under review. VRC 011 (06-I-0149) is a Phase I study to evaluate the intramuscular, subcutaneous and intradermal routes of administration for priming vaccinations with either three injections of the 6-plasmid DNA vaccine or one injection of the rAd5 vaccine. In all schedules a rAd5 booster injection is administered IM. Sixty subjects were enrolled; equal numbers of subjects had negative and positive antibody titers to adenovirus serotype 5 at enrollment in order to gain a better understanding of whether pre-existing antibody affects the safety and immunogenicity of the regimens. Follow-up of study participants was completed during FY 09. VRC 012 (07-I-0167) is 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 the Part I enrollments and vaccinations were completed. The enrollments and study vaccinations for Part II of the study are ongoing in FY09. VRC 015 (08-I-0171) is 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. The enrollments and study vaccinations are ongoing during FY09. HVTN 505 (09-I-0163) is a multicenter Phase II 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 I/II safety and immunogenicity evaluations of the vaccines were completed, this study was developed to begin a new phase of evaluation. It is designed to see whether or not the vaccines have an effect on HIV viral load in vaccine recipients as compared to placebo recipients who later acquire HIV infection during about 3 years of follow-up.

摘要：该临床研究项目是在 NIH 临床中心 VRC 诊所进行的与预防性 HIV 疫苗相关的临床试验。这些包括评估候选预防性 HIV-1 疫苗的筛选方案和临床试验，包括：DNA 疫苗构建体、重组腺病毒载体血清型 5 (rAd5) 疫苗和重组腺病毒载体血清型 35 (rAd35) 疫苗。研究旨在评估剂量、免疫原性、给药途径、给药装置和初免-加强方案。迄今为止每项研究的简要总结如下。 筛选方案 VRC 000 (02-I-0127) 有助于招募和筛选健康的 HIV 阴性受试者，以进行预防性 HIV 疫苗临床试验。在参加研究之前，将审查有关疫苗的教育材料并将其提供给受试者。 在 VRC 诊所成立之前，通过与其他校内研究人员合作，对 VRC 开发的 B 进化枝单质粒 DNA 疫苗进行了 I 期研究 VRC 001 (01-I-0079)。 描述结果的手稿发表在 FY07 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。 2007 财年，一份描述结果的手稿发表于 J Infect Dis, 2006. 194(12): p. 11。 1650-60。该方案的长期随访于 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。 2007 财年，一份描述结果的手稿发表于 J Infect Dis, 2006. 194(12): p. 11。 1638-49。该方案的长期随访于 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。 2007 财年，发表了一份描述研究结果的手稿《疫苗》，2007 年。 25(20)：第 17 页。 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。该研究的目的是在入组时招募相同数量的腺病毒血清型 5 抗体滴度低和高的受试者，以便更好地了解预先存在的抗体是否影响 rAd5 加强剂的安全性和免疫原性。 2008 财年第 94 周完成了长期随访评估，并完成了主要免疫原性测定的分析。 VRC 009 (05-I-0081) 是一项 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。 2007 财年期间，该研究的统计分析已完成，VRC 009 和 010 合并的研究结果手稿正在审查中。 VRC 010 (05-I-0140) 是一项 rAd5 疫苗的 I 期研究，作为 VRC 007 研究中先前接种过 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。 2007 财年期间，该研究的统计分析已完成，VRC 009 和 010 合并的研究结果手稿正在审查中。 VRC 011 (06-I-0149) 是一项 I 期研究，旨在评估通过注射 3 次 6 质粒 DNA 疫苗或注射 1 次 rAd5 疫苗进行预接种的肌内、皮下和皮内给药途径。 在所有方案中，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，以便更好地了解先前存在的抗体是否影响治疗方案的安全性和免疫原性。研究参与者的随访于 2009 财年完成。 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，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工作将于 2009 财年进行。 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。 2009 财年期间，招募和研究疫苗接种工作正在进行中。 HVTN 505 (09-I-0163) 是 VRC 候选 DNA prime-rAd5 增强 HIV 疫苗方案的多中心 II 期研究，VRC 临床试验核心作为站点参与其中。在疫苗的I/II期安全性和免疫原性评估完成后，开展本研究以开始新阶段的评估。它的目的是观察与安慰剂接受者相比，疫苗是否对疫苗接受者的 HIV 病毒载量产生影响，而安慰剂接受者后来在大约 3 年的随访期间感染了 HIV。