Addressing unanticipated events for Intranasal Influenza H5 Vaccine Trial

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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.