AND INTRODUCTION: The Vaccine Research Center (VRC) is dedicated to translating basic science knowledge into clinical vaccine products. This requires the ability to carry out basic research, construct new vaccine products, perform preclinical research and evaluate candidate vaccines in human studies. To conduct human clinical trials, the VRC has established the infrastructure to produce vaccine products using good manufacturing practices, and to manage regulatory issues related to human trials. The public health burden of influenza in the USA is enormous. The Centers for Disease Control and Prevention (CDC) estimates that between 5% to 20% of the U.S. population is infected each year (www.cdc.gov/flu/about/disease/index.htm), leading to more than 200,000 hospitalizations and 41,000 deaths . If these figures are extrapolated to the rest of the world, the average global burden of inter-pandemic influenza may be on the order of approximately 1 billion cases of flu, roughly 3 to 5 million cases of severe illness and up to half a million deaths annually . A recent spread of potentially pandemic highly pathogenic H5N1 subtype and a novel swine origin H1N1 subtype that already became pandemic has raised serious concerns about influenza vaccine supply in a pandemic situation when the currently available production methodology would be unable to meet worldwide public health demands. Also, antigen evolution in pandemic may necessitate a more agile, rapidly scalable production process. With recent emergence of a new pandemic influenza virus, the methodology and timeline for the vaccine development and production has become an urgent issue. It takes more than six months from identification of a pandemic influenza strain to production of the first doses of vaccine using licensed technology. Delays in traditional vaccine production could result from poor growth of the virus strain used to make the vaccine. Recombinant DNA technologies allow much faster development and production of the vaccine candidates that are based on viral genome sequences. Plasmid DNA-based vaccines have demonstrated preclinical efficacy combined with fast and relatively easy manufacturing processes. The plasmid DNA vaccines can be quickly modified to carry an antigen for which immune response is desired. This process is more efficient than the cumbersome, costly and lengthy traditional processes involved with inactivation, purification, and concentration of native or modified HA antigens. The disadvantage of current DNA vaccines is that it may take several injections to generate an immune response with a magnitude and durability considered adequate for protection. Therefore beyond the proof of concept aspect demonstrating ability to rapidly produce a vaccine, further development of ways to induce a desirable immune response by a single immunization may be needed in the future. An increased magnitude and broadened immune responses to DNA vaccines could also be achieved by using a prime-boost strategy. Testing potential vaccine candidates in clinical studies may provide urgently needed data on immunogenicity of these novel influenza vaccine formulations and clarify if they may offer cross-protection in a swiftly emerging world of new antigenically distinct influenza viruses. SCOPE: The purpose of this project is to support various VRC Universal Influenza studies. Activities include: the provision of support services in all three areas outlined. Specifically, for each population cohort identified), this project will require the provision of all necessary technical, clinical, and management services in order to support two (2) phase-I clinical trials, one (1) phase-II clinical trial, and one (1) natural history and sample collection trial for antibody assay development and licensed influenza immunology. TECHNICAL ACTIVITIES: Activities of this project include the following areas: Area 1: Coordinating Clinical Site Selection and Conduct of Vaccine Clinical Trials 1. Site Selection and Acquisition 2. Recruitment, Retention, and Follow-up 3. Study Data 4. Testing and Study Specimen Management Area 2: Electronic Data Management Services Area 3: Regulatory Support and Clinical Monitoring 1. Regulatory Support 2. Clinical Monitoring
