Development of a Bacterial Ghost DNA vaccine for Influenza using antibody epitope

描述(申请人提供)：流感流行和大流行是对人类健康的主要威胁。接种疫苗是控制年度和新发流感大流行的主要战略。目前的流感疫苗平台和生产系统缺乏灵活性、速度慢、价格昂贵，而且不能对新出现的病毒株做出快速反应。因此，迫切需要快速开发和生产流感疫苗的新技术。考虑到这些挑战，这项提案旨在证明实施疫苗战略的可行性，该战略结合了细菌幽灵、DNA微环和基于蛋白质组学的抗体表位映射等新技术。蛋白质组学技术将被用来利用暴露于H1蛋白或含有H1病毒的动物的血清来快速鉴定流感H1蛋白中的抗体结合表位。由此产生的表位将用于开发和生产具有固定化微环DNA结构的细菌幽灵疫苗。细菌幽灵最近被用作DNA微环疫苗的载体和刺激物，取得了良好的效果。DNA微环消除了用质粒DNA接种疫苗所涉及的许多风险，并在一步低成本的生产过程中被结合到BG中。动物将接受使用生产的细菌幽灵疫苗的预定疫苗接种计划，并将评估免疫反应。

DESCRIPTION (provided by applicant): Influenza epidemics and pandemics are major threats to human health. Vaccination is the primary strategy for the control of annual and emerging influenza pandemics. Present influenza vaccine platforms and production systems are inflexible, slow, expensive, and cannot rapidly respond to an emerging strain of virus. Thus, new technologies for the rapid development and production of influenza vaccines are urgently needed. With these challenges in mind this proposal is aimed at demonstrating the feasibility of implementing a vaccine strategy combining the novel technologies of Bacterial Ghosts, DNA minicircles, and proteomics-based antibody epitope mapping. Proteomics technologies will be used to rapidly identify antibody binding epitopes in the influenza H1 protein using sera from animals exposed to H1 protein or H1 containing virus. The resulting epitopes will be used to develop and produce Bacterial Ghost vaccines with immobilized minicircle DNA constructs. Bacterial Ghosts have recently been used as carriers and stimulators of DNA minicircle vaccines with promising results. DNA minicircles eliminate many of the risks involved in vaccination with plasmid DNA and are incorporated into BG in a one-step low cost production process. Animals will undergo a scheduled vaccination scheme using the produced Bacterial Ghost vaccines and the immune response will be assessed.