Addressing unanticipated events for Intranasal Influenza H5 Vaccine Trial

项目总结/摘要 季节性流感疾病的负担，大流行的持续威胁，以及目前的不足， 流感疫苗强调迫切需要改进的流感疫苗。疫苗可以刺激 粘膜免疫系统是一种有前途的方法，因为上呼吸道粘膜充当了 因为流感特异性粘膜抗体与流感相关， 预防有了这个建议，我们将进一步了解粘膜免疫反应的鼻内 流感疫苗。我们的目标是建立一个原理证明，一种新的粘膜H5 N1疫苗（BW- 1014）是安全的，并且可以诱导粘膜免疫应答。BW-1014为纳米乳剂佐剂 鼻内施用重组H5流感疫苗。我们将评估BW-1014在三个不同的剂量下给药， 含纳米乳剂佐剂的抗原剂量、作为活性对照的仅抗原制剂和安慰剂 作为一个不活跃的比较者。18 - 39岁的志愿者将接种两次研究疫苗 第1天和第29天。随后，所有志愿者将接受许可的胃肠外流感病毒疫苗， H5 N1（与初级系列异源）作为第197天的加强剂量。参与者将被跟踪13 他们将在几个时间点提供血液和鼻洗液样本， 体液、细胞介导和粘膜免疫测定。试验的目的是为了获得有价值的信息 关于粘膜疫苗接种的免疫反应，同时最大限度地减少新疫苗对志愿者的风险， 第一次给人类。这些是项目研究的目标： 1.评估鼻内BW-1014的安全性和耐受性 第二章.评估鼻内BW-1014的粘膜免疫应答 第三章.检查对鼻内BW-1014的初始系列的免疫应答，随后进行加强免疫 异源非肠道H5 N1疫苗的剂量 这些研究目标将在根据当地标准进行的临床试验中进行评估。 法律的和监管要求、适用的美国联邦法规、ICH指南和药物临床试验质量管理体系 实践（GCP）标准。我们有一个确保临床监测、持续质量管理的计划， 质量保证和质量控制活动、外部独立安全监督和数据管理。

Project Summary/Abstract The burden of seasonal influenza illness, the continuing threat of a pandemic, and the inadequacy of current influenza vaccines emphasize the urgent need for improved influenza vaccines. Vaccines that stimulate the mucosal immune system are a promising approach because the upper respiratory mucosa serves as the primary site of infection and because influenza-specific mucosal antibodies are associated with influenza prevention. With this proposal, we will advance the understanding of mucosal immune response to intranasal influenza vaccination. Our goal is to establish a proof-of-principle that a novel mucosal H5N1 vaccine (BW- 1014) is safe and can induce a mucosal immunologic response. BW-1014 is nanoemulsion-adjuvanted recombinant H5 influenza vaccine administered intranasally. We will evaluate BW-1014 given at three different antigen doses with nanoemulsion adjuvant, an antigen only formulation as an active comparator, and placebo as an inactive comparator. Two vaccinations of study vaccine will be given to volunteers aged 18 through 39 years on days 1 and 29. Subsequently, all volunteers will receive licensed, parenteral Influenza Virus Vaccine, H5N1 (heterologous to the primary series) as a booster dose on day 197. Participants will be followed for 13 months for safety outcomes, and they will provide blood and nasal wash specimens at several time points for humoral, cell-mediated, and mucosal immune assays. The trial is designed to generate valuable information about the immune responses to mucosal vaccination while minimizing the risk to volunteers of a new vaccine given to humans for the first time. These are the project research aims:  Aim 1. Assess the safety and tolerability of intranasal BW-1014  Aim 2. Assess the mucosal immune response of intranasal BW-1014  Aim 3. Examine the immune response to a primary series of intranasal BW-1014 followed by a boosting dose of heterologous parenteral H5N1 vaccine These research aims will be assessed within the context of a clinical trial to be conducted according to local legal and regulatory requirements, applicable US federal regulations, ICH guidelines, and Good Clinical Practice (GCP) standards. We have a plan for ensuring clinical monitoring, ongoing quality management with quality assurance and quality control activities, external independent safety oversight, and data management.