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

基本信息

批准号：
10678885
负责人：
Justin R. Ortiz
金额：
$ 11.35万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
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/10678885
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 Interferon Type II Interleukin-10 Interleukin-2 Interleukin-4 Intramuscular Intranasal Administration Legal Licensing Measurable Measurement Measures Mediating Memory Memory B-Lymphocyte Modeling Monitor Mucosal Immune Responses Mucosal Immune System Mucosal Immunity Mucous Membrane Mus Nasal Lavage Fluid 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 inhibiting antibody 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 assessment safety outcomes seasonal influenza vaccine response vaccine trial volunteer

项目摘要

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.

项目摘要/摘要季节性影响力的伯恩（Burnen），流行病的持续威胁和当前的不足影响力疫苗强调迫切需要改善影响力疫苗。刺激疫苗粘膜免疫系统是一种有前途的方法，因为上呼吸道粘膜是主要感染部位，并且因为影响特异性粘膜抗体与影响力有关预防。通过此建议，我们将提高对粘膜免疫反应对鼻内的反应的理解影响力疫苗接种。我们的目标是建立一种新型粘膜H5N1疫苗接种的原则证明（BW- 1014）是安全的，可以诱导粘膜免疫反应。 BW-1014是纳米乳剂 - 辅助重组H5影响了鼻内给药的疫苗。我们将评估以三种不同的方式评估BW-1014 可调节纳米乳剂的抗原剂量，仅作为活性比较剂的抗原公式和安慰剂作为无活动的比较器。研究疫苗的两种疫苗将向18至39岁的志愿者提供在第1天和第29天的年份。随后，所有志愿者都将获得许可的父母流感病毒疫苗， H5N1（主要系列异源）是第197天的助推器剂量。将跟踪参与者13 确保结局的月份，它们将在几个时间点提供血液和鼻清洗标本体液，细胞介导的和粘膜免疫测定。该试验旨在生成有价值的信息关于对粘膜疫苗的免疫反应，同时最大程度地减少对新疫苗的志愿者的风险第一次给予人类。这些是项目研究目的： 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。检查对一系列鼻内BW-1014的免疫响应，然后提高异源肠胃外H5N1疫苗的剂量这些研究目标将在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指南和良好的临床练习（GCP）标准。我们有一个计划，以确保与临床监测，持续的质量管理质量保证和质量控制活动，外部独立安全监督以及数据管理。