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：该临床研究项目是针对NIH临床中心VRC诊所进行的与预防性HIV疫苗有关的临床试验。这些由筛查方案和临床试验组成，以评估候选预防性HIV-1疫苗，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35（RAD35）疫苗。研究旨在评估剂量，免疫原性，给药途径，用于给药的装置和原始方案。迄今为止的每项研究的简要摘要如下。 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，用于研究性预防性HIV HIV疫苗临床试验。在入学研究之前，对疫苗的教育材料进行了审查并提供给受试者。 在建立VRC诊所之前，I阶段研究的VRC 001（01-I-I-0079）通过VRC开发的单质粒DNA疫苗是通过与其他室内研究人员的合作进行的。 一个描述结果WSS的手稿在07财年发表在J获取免疫缺陷症状，2007。44（5）：p。 601-5。 VRC 004（03-I-0022）是多层4质粒DNA疫苗的第一阶段临床试验，VRC-HIVDNA009-00-VP，该试验表达了来自进化核武器B HIV-1和ENK糖蛋白的GAG-POL-NEF多蛋白，该研究来自Callades A，B and b and b and b and C.该研究。在07财年，描述结果的手稿发表了J Infect Dis，2006。194（12）：p。 1650-60。该协议的长期随访于2008财年完成。 VRC 006（04-I-0128）是研究重组血清型5腺病毒载体（RAD5）疫苗，VRC-HIVADV014-00-VP的第一阶段临床试验，用于预防HIV感染。该疫苗由4个腺病毒载体（在3：1：1：1的比例中）组成，该疫苗分别从进化枝A，B和C分别编码了来自进化枝B和HIV-1 ENV糖蛋白的HIV-1 GAG/POL多蛋白。这项研究评估了三种剂量。在07财年，描述结果的手稿发表了J Infect Dis，2006。194（12）：p。 1638-49。该协议的长期随访于2009财年完成。 VRC 007（04-I-I-0254）是多层6-质量HIV-1 DNA疫苗的第一阶段临床试验，VRC-HIVDNA016-00-VP，该试验表达了从进化枝BHIV-1和C. b and b and b and b and b and b and b and b and b and b and b and b and b and b and b and b and b and b and C.在2007财年，描述研究结果的手稿发表了疫苗，2007年。25（20）：p。 4085-92。 VRC 008（05-I-0148）是对促进疫苗接种方案的第一阶段研究，该研究由3种疫苗和6倍磷酸DNA疫苗的疫苗组成，然后用RAD5疫苗促进。这项研究评估了生物体和针/注射器作为DNA疫苗的注射装置的安全性和免疫原性，以及RAD5助推器的两种不同剂量的安全性和免疫原性。该研究旨在注册对腺病毒血清型5的低抗体滴度的相等数量的受试者，以便更好地了解既有抗体是否影响RAD5助推器的安全性和免疫原性。在08周期间，完成了94次长期随访评估，并完成了主要免疫原性测定法。 VRC 009（05-I-0081）是对RAD5疫苗的I期研究，作为先前在VRC 004研究中用4 mg或8 mg剂量的4倍剂多叶片DNA疫苗接种的受试者中的促进疫苗接种。十个主题被录取。在07财年期间，对研究的统计分析完成了，正在审查VRC 009和010的研究结果的手稿。 VRC 010（05-I-0140）是对RAD5疫苗作为I阶段研究，作为先前用4 mg的6倍粒多叶片多叶片DNA DNA疫苗在VRC 007研究中免疫的受试者中的促进疫苗接种。只有少数受试者有资格参加； 4个受试者招收并完成了24周的随访。 在07财年期间，对研究的统计分析完成了，正在审查VRC 009和010的研究结果的手稿。 VRC 011（06-I-0149）是一项I期研究，用于评估肌肉内，皮下和皮内给药途径，用于启动疫苗接种疫苗，并注射了三种6-铂DNA疫苗或一种注射RAD5疫苗的疫苗。 在所有时间表中，对RAD5助推器注入均被施用IM。六十名受试者被录取；相等数量的受试者在入学时具有对腺病毒血清型5的阴性和阳性抗体滴度，以便更好地了解既有抗体是否影响该方案的安全性和免疫原性。在09财年期间完成了研究参与者的随访。 VRC 012（07-I-0167）是一项I阶段研究，用于评估一项研究的三个剂量的新型原型腺病毒载体血清型35疫苗35疫苗（RAD 35-ENVA），在研究的第一部分中，然后在研究的第二部分中，在研究的第二部分中，具有RAD5-ENVA疫苗的异源原料时间表。在2008财年期间，I部分入学率和疫苗接种完成。 该研究第二部分的入学疫苗和研究疫苗在09财年正在进行。 VRC 015（08-I-0171）是一项I期研究，旨在评估生物体和针/注射器的安全性和免疫原性，作为重组血清型5腺病毒载体（RAD5）疫苗的注射装置，VRC-HIVADV014-00-VP。 在09财年期间，入学疫苗和研究疫苗正在进行中。 HVTN 505（09-I-0163）是VRC候选DNA Prime-Rad5促进HIV疫苗方案的多中心II期研究，VRC临床试验核心正在作为站点参与该方案。在完成了I/II阶段的安全性和免疫原性评估后，已开发了这项研究以开始新的评估阶段。与安慰剂接受者相比，它旨在查看疫苗是否对疫苗受体中的HIV病毒负荷有影响，而安慰剂接受者后来在随访的大约3年中获得了HIV感染。