ARRA: Clinical Support for Universal Influenza Development

ARRA：对通用流感发展的临床支持

• 批准号: 8157125
• 负责人: Barney Graham
• 金额: $ 865.48万
• 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/8157125
• 关键词: Clinical; Development; Influenza

BACKGROUND AND INTRODUCTION: The Vaccine Research Center (VRC) is dedicated to translating basic science knowledge into clinical vaccine products. This requires the ability to carry out basic research, construct new vaccine products, perform preclinical research and evaluate candidate vaccines in human studies. To conduct human clinical trials, the VRC has established the infrastructure to produce vaccine products using good manufacturing practices, and to manage regulatory issues related to human trials. The public health burden of influenza in the USA is enormous. The Centers for Disease Control and Prevention (CDC) estimates that between 5% to 20% of the U.S. population is infected each year (www.cdc.gov/flu/about/disease/index.htm), leading to more than 200,000 hospitalizations and 41,000 deaths . If these figures are extrapolated to the rest of the world, the average global burden of inter-pandemic influenza may be on the order of approximately 1 billion cases of flu, roughly 3 to 5 million cases of severe illness and up to half a million deaths annually . A recent spread of potentially pandemic highly pathogenic H5N1 subtype and a novel swine origin H1N1 subtype that already became pandemic has raised serious concerns about influenza vaccine supply in a pandemic situation when the currently available production methodology would be unable to meet worldwide public health demands. Also, antigen evolution in pandemic may necessitate a more agile, rapidly scalable production process. With recent emergence of a new pandemic influenza virus, the methodology and timeline for the vaccine development and production has become an urgent issue. It takes more than six months from identification of a pandemic influenza strain to production of the first doses of vaccine using licensed technology. Delays in traditional vaccine production could result from poor growth of the virus strain used to make the vaccine. Recombinant DNA technologies allow much faster development and production of the vaccine candidates that are based on viral genome sequences. Plasmid DNA-based vaccines have demonstrated preclinical efficacy combined with fast and relatively easy manufacturing processes. The plasmid DNA vaccines can be quickly modified to carry an antigen for which immune response is desired. This process is more efficient than the cumbersome, costly and lengthy traditional processes involved with inactivation, purification, and concentration of native or modified HA antigens. The disadvantage of current DNA vaccines is that it may take several injections to generate an immune response with a magnitude and durability considered adequate for protection. Therefore beyond the proof of concept aspect demonstrating ability to rapidly produce a vaccine, further development of ways to induce a desirable immune response by a single immunization may be needed in the future. An increased magnitude and broadened immune responses to DNA vaccines could also be achieved by using a prime-boost strategy. Testing potential vaccine candidates in clinical studies may provide urgently needed data on immunogenicity of these novel influenza vaccine formulations and clarify if they may offer cross-protection in a swiftly emerging world of new antigenically distinct influenza viruses. SCOPE: The purpose of this project is to support various VRC Universal Influenza studies. Activities include: the provision of support services in all three areas outlined. Specifically, for each population cohort identified), this project will require the provision of all necessary technical, clinical, and management services in order to support two (2) phase-I clinical trials, one (1) phase-II clinical trial, and one (1) natural history and sample collection trial for antibody assay development and licensed influenza immunology. TECHNICAL ACTIVITIES: Activities of this project include the following areas: Area 1: Coordinating Clinical Site Selection and Conduct of Vaccine Clinical Trials 1. Site Selection and Acquisition 2. Recruitment, Retention, and Follow-up 3. Study Data 4. Testing and Study Specimen Management Area 2: Electronic Data Management Services Area 3: Regulatory Support and Clinical Monitoring 1. Regulatory Support 2. Clinical Monitoring

背景和简介： 疫苗研究中心（VRC）致力于将基础科学知识转化为临床疫苗产品。这就需要能够进行基础研究，建造新的疫苗产品，进行临床前研究并评估人类研究中的候选疫苗。为了进行人类的临床试验，VRC建立了使用良好的制造实践生产疫苗产品的基础设施，并管理与人类试验有关的监管问题。 美国流感的公共卫生负担巨大。疾病控制与预防中心（CDC）估计，每年感染5％至20％的人口（www.cdc.gov/flu/about/disease/index.htm），导致超过200,000的住院和41,000人死亡。如果将这些数字推送到世界其他地区，那么流行流感流感流感的全球平均负担可能处于大约10亿病例的流感范围内，大约3至500万例严重疾病病例，每年高达50万人死亡。 在当前可用的生产方法将无法满足全球公共卫生需求时，可能已经成为大流行的可能大流行的高度致病性H5N1亚型和一种新型的猪H1N1亚型的扩散引起了人们对流行疫苗供应的严重关注。同样，大流行中的抗原进化可能需要更敏捷，迅速扩展的生产过程。随着新的大流行性流感病毒的出现，疫苗开发和生产的方法和时间表已成为一个紧迫的问题。从鉴定大流行性流感菌株到使用许可技术的第一剂疫苗的生产，需要六个月以上的时间。传统疫苗生产的延迟可能是由于用于制造疫苗的病毒菌株生长不良而导致的。重组DNA技术允许基于病毒基因组序列的疫苗候选物的更快开发和生产。基于质粒DNA的疫苗已经证明了临床前疗效，结合了快速和相对容易的制造工艺。可以快速修饰质粒DNA疫苗以携带需要免疫反应的抗原。 该过程比与原生或改良的HA抗原相关的繁琐，昂贵和冗长的传统过程更有效。 当前DNA疫苗的缺点是，可能需要几次注射才能产生一种免疫反应，其幅度和耐用性被认为是足够的保护。因此，除了概念方面的证明表明能够快速生产疫苗的能力之外，将来可能需要进一步发展通过单一免疫来诱导理想的免疫反应的方法。也可以通过使用Prime-Boost策略来实现对DNA疫苗的幅度增加和对DNA疫苗的免疫反应。 在临床研究中测试潜在的候选疫苗可能会提供有关这些新型流感疫苗配方的免疫原性的急需数据，并阐明它们是否可以在新的新兴抗原抗原不同流感病毒的世界中提供交叉保护。 范围： 该项目的目的是支持各种VRC通用流感研究。活动包括：在所有三个领域提供支持服务。具体而言，对于确定的每个人群），该项目将需要提供所有必要的技术，临床和管理服务，以支持两（2）阶段IS期临床试验，一（1）个II期临床试验以及一（1）个自然历史和样本收集试验，用于抗体分析开发和持牌型流感型型型型型型型型临床试验。 技术活动： 该项目的活动包括以下领域： 区域1：协调临床部位选择和疫苗临床试验的行为 1。现场选择和获取 2。招募，保留和随访 3。研究数据 4。测试和研究标本管理 区域2：电子数据管理服务 区域3：监管支持和临床监测 1。监管支持 2。临床监测