HIV-1 Vaccine Based on Chimp Serotypes of Adenovirus

基于黑猩猩腺病毒血清型的 HIV-1 疫苗

• 批准号: 8514890
• 负责人: Hildegund C. J. Ertl
• 金额: $ 215.51万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514890
• 关键词: AIDS vaccine development; Adenovirus Vector; Adenoviruses; Africa; Animals; Antigens; Characteristics; Clinical; Clinical Trials; Development; Disease; Dose; Future; Gagging; Goals; HIV Vaccine Trials Network; HIV vaccine; HIV-1; Human; Immune; Immune response; Infection; Modeling; National Institute of Allergy and Infectious Disease; Pan Genus; Performance; Phase; Phase I Clinical Trials; Pre-Clinical Model; Prevalence; Regimen; Research; Serotyping; Staging; T cell response; T-Lymphocyte; Vaccines; base; cohort; immunogenicity; pathogen; programs; safety testing; vaccine candidate; vector; AIDS vaccine development; Adenovirus Vector; Adenoviruses; Africa; Animals; Antigens; Characteristics; Clinical; Clinical Trials; Development; Disease; Dose; Future; Gagging; Goals; HIV Vaccine Trials Network; HIV vaccine; HIV-1; Human; Immune; Immune response; Infection; Modeling; National Institute of Allergy and Infectious Disease; Pan Genus; Performance; Phase; Phase I Clinical Trials; Pre-Clinical Model; Prevalence; Regimen; Research; Serotyping; Staging; T cell response; T-Lymphocyte; Vaccines; base; cohort; immunogenicity; pathogen; programs; safety testing; vaccine candidate; vector

This program focuses on vaccine candidates for HIV-1 based on two replication-defective chimpanzee (chimp) adenovirus (Ad) vectors, termed AdC6 and AdC7. The program has four interlinked goals. Our first goal is to pursue clinical development of AdC6 and AdC7 vectors expressing gag of HIV-1 to test the safety of each vector in dose-escalation phase I trials, and to assess the immunogenicity of both vectors combined in a heterologous prime boost regimen in a phase IIA trial. Clinical trials will be conducted under the auspices of the NIAID-sponsored HIV Vaccine Trials Network (HVTN). Our second goal is to further optimize the AdC6 and AdC7 vectors for later stage clinical trials. Our third goal is a research objective to define the quality of T cell responses to AdC6/AdC7 prime boost regimens in both experimental animals and human vaccine recipients. Evidence is mounting that different vaccine regimens not only influence the magnitude but also the quality of the ensuing cellular immune responses, and that this quality substantially influences progression of HIV-1 infections toward disease. Vaccine-induced correlates of protection against HIV-1 associated illness remain poorly defined, which has made it difficult to compare the clinical potential of the vectors considered as platforms for a candidate HIV vaccine. We aim to carefully define pertinent characteristics of the cellular immune responses elicited by chimp Ad vector prime boost regimens in preclinical models, and how such characteristics correlate with protection against challenge with model pathogens. Our fourth goal is to elucidate the effect of pre-existing T cells to conserved antigens of Ads on the performance of chimp Ad vectors as vaccine carriers. The prevalence of such T cells will be determined in human cohorts from the US and Africa. Their effect on vaccine-induced T cell responses will first be assessed in experimental animals and then in human vaccine recipients. Definition of the characteristics of effective immune responses in animals with comparison studies in human vaccine recipients will advance our understanding of the correlates of immune protection to be pursued in future efforts of AIDS vaccine development.

该计划的重点是基于两个复制缺陷的黑猩猩（Chimp）腺病毒（AD）向量的HIV-1疫苗候选物，称为ADC6和ADC7。该计划具有四个相互联系的目标。我们的第一个目标是追求表达HIV-1的ADC6和ADC7矢量的临床开发，以测试在剂量降低I期试验中每个向量的安全性，并评估两个矢量在IIA期试验中的异源Prime Boost方案中组合的矢量的免疫原性。临床试验将在NIAID赞助的HIV疫苗试验网络（HVTN）的主持下进行。我们的第二个目标是进一步优化ADC6和ADC7向量以进行后期临床试验。我们的第三个目标是确定实验动物和人疫苗接种者中T细胞反应质量的质量。有证据表明，不同的疫苗方案不仅会影响随之而来的细胞免疫反应的大小，而且会影响这种质量，并且这种质量显着影响HIV-1感染对疾病的发展。疫苗诱导的针对HIV-1相关疾病的保护相关性仍然很差，这使得很难比较被认为是候选HIV疫苗平台的向量的临床潜力。我们的目标是仔细定义临床前模型中科植物AD矢量质量增强方案引起的细胞免疫反应的相关特征，以及这种特征与模型病原体的挑战的保护如何相关。我们的第四个目标是阐明预先存在的T细胞对ADS保守的抗原对黑猩猩AD载体作为疫苗载体的性能的影响。此类T细胞的患病率将在美国和非洲的人类人群中确定。它们对疫苗诱导的T细胞反应的影响将首先在实验动物中，然后在人类疫苗接受者中进行评估。通过对人类疫苗接收者进行比较研究的动物有效免疫反应特征的定义将促进我们对艾滋病疫苗开发的未来努力中应追求的免疫保护相关性的理解。