Addressing unanticipated events for Intranasal Influenza H5 Vaccine Trial

解决鼻内流感 H5 疫苗试验的意外事件

• 批准号: 10620369
• 负责人: Justin R. Ortiz
• 金额: $ 16.74万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10620369
• 关键词: Address; Adjuvant; Adult; Adverse event; Antibodies; Antibody Response; Antigens; B-Lymphocytes; Biological Assay; Blood; CD8-Positive T-Lymphocytes; Cell surface; Cells; Cellular Immunity; Clinical; Clinical Trials; Dose; Double-Blind Method; Enrollment; Ensure; Enzyme-Linked Immunosorbent Assay; Evaluation; Event; Ferrets; Flow Cytometry; Formulation; Frequencies; Goals; Good Clinical Practice; Granzyme; Guidelines; Hemagglutination; Human; Immune response; Immunity; Immunoassay; Immunoglobulin A; Immunoglobulin G; Immunologics; Immunology procedure; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A virus; Influenza prevention; Influenza vaccination; Intention; Interferons; Interleukin-10; Interleukin-2; Interleukin-4; Intramuscular; Legal; Measurable; Measurement; Measures; Mediating; Memory; Memory B-Lymphocyte; Modeling; Monitor; Mucosal Immune Responses; Mucosal Immune System; Mucosal Immunity; Mucous Membrane; Mus; Nose; Participant; Phenotype; Phylogenetic Analysis; Placebo Control; Placebos; Quality Control; Randomized; Recombinants; Regulation; Research Project Grants; Respiratory Mucosa; Route; Safety; Sample Size; Secretory Immunoglobulin A; Series; Serum; Signal Transduction; Site; Specimen; Stains; T memory cell; T-Lymphocyte; TNF gene; TNFSF5 gene; Time; United States National Institutes of Health; Vaccination; Vaccine Adjuvant; Vaccine Research; Vaccines; Viral; Virus; active comparator; aged; booster vaccine; cell mediated immune response; chemokine; cytokine; data management; design; first-in-human; immunogenicity; improved; influenza virus vaccine; interleukin-21; mucosal vaccination; mucosal vaccine; nanoemulsion; neutralizing antibody; novel; novel vaccines; pandemic disease; phase I trial; pre-clinical; preclinical study; prevent; quality assurance; response; risk minimization; safety outcomes; seasonal influenza; vaccine response; vaccine trial; volunteer

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.

项目概要/摘要 季节性流感疾病的负担、大流行的持续威胁以及当前的不足 流感疫苗强调迫切需要改进流感疫苗。 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 主要感染部位，因为流感特异性粘膜抗体与流感相关 通过这项建议，我们将增进对鼻内粘膜免疫反应的理解。 我们的目标是建立一种新型粘膜 H5N1 疫苗（BW-）的原理验证。 1014）是安全的，可以诱导粘膜免疫反应 BW-1014 是纳米乳剂佐剂。 我们将评估鼻内注射的重组 H5 流感疫苗的三种不同给药方式。 含有纳米乳佐剂的抗原剂量、作为活性比较剂的仅抗原制剂和安慰剂 作为非活跃对照者，将为 18 至 39 岁的志愿者接种两次研究疫苗。 第 1 天和第 29 天。随后，所有志愿者将获得获得许可的注射流感病毒疫苗， H5N1（与主要系列异源）在第 197 天作为加强剂量。参与者将被跟踪 13 几个月的安全结果，他们将在几个时间点提供血液和鼻洗样本 该试验旨在产生有价值的信息。 关于粘膜疫苗接种的免疫反应，同时最大限度地降低新疫苗对志愿者的风险 这些是首次给予人类的项目研究目标： 目标 1. 评估鼻内 BW-1014 的安全性和耐受性 目标 2. 评估鼻内 BW-1014 的粘膜免疫反应 目标 3. 检查对鼻内 BW-1014 的初级系列以及随后的加强免疫反应 异源肠外 H5N1 疫苗剂量 这些研究目标将在根据当地情况进行的临床试验的背景下进行评估 法律和监管要求、适用的美国联邦法规、ICH 指南和 Good Clinical 我们制定了确保临床监测和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。