Addressing unanticipated events for Intranasal Influenza H5 Vaccine Trial

项目摘要/摘要 季节性流感疾病的负担，大流行的持续威胁，以及当前疫情的不足 流感疫苗强调迫切需要改进的流感疫苗。刺激人类健康的疫苗 粘膜免疫系统是一种很有前途的方法，因为上呼吸道粘膜是 主要感染部位，因为流感特异性粘膜抗体与流感有关 预防。通过这一建议，我们将促进对鼻腔粘膜免疫反应的理解。 接种流感疫苗。我们的目标是建立一种新的粘膜H5N1疫苗(BW-BW)的原理证明。 1014)是安全的，并能诱导粘膜免疫反应。BW-1014是纳米乳剂佐剂 重组H5流感疫苗鼻腔注射。我们将评估BW-1014在三个不同的 纳米乳剂佐剂的抗原剂量，作为活性比较物的仅抗原配方，以及安慰剂 作为一个不活跃的比较器。将为18至39岁的志愿者接种两种研究疫苗 年份在第1天和第29天。随后，所有志愿者将接种获得许可的非肠道流感病毒疫苗， H5N1(与初级系列不同)作为第197天的加强剂。参与者将被跟踪13年 几个月的安全结果，他们将在几个时间点提供血液和鼻腔冲洗样本 体液免疫、细胞免疫和粘膜免疫分析。这项试验旨在产生有价值的信息 关于黏膜疫苗接种的免疫反应，同时将新疫苗对志愿者的风险降至最低 第一次给了人类。以下是本课题的研究目标： 目标1.评估鼻用BW-1014的安全性和耐受性 目的2.评估鼻腔注射BW-1014后的黏膜免疫应答 目标3.检查一系列鼻腔注射BW-1014后的免疫反应 异种H5N1肠外疫苗的剂量 这些研究目标将在临床试验的范围内进行评估，该试验将根据当地的 法律和法规要求、适用的美国联邦法规、非物质文化遗产指南和良好临床 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.