Development of an improved intranasal vaccine against influenza

尽管开发了几种类型的流感疫苗(减毒活疫苗、灭活疫苗、亚单位疫苗)，但世界 卫生组织估计，季节性流感仍导致300-500万例严重疾病 每年有29万到65万人死亡。尽管疫苗接种计划有助于降低发病率 和季节性流感相关的死亡率，目前的疫苗方法受到劣质疫苗的限制- 免疫调节和疫苗接种率低。克服对流感的次优免疫反应 在疫苗接种方面，我们开发了一种先进的基于过氧化氢的定点氧化技术 使病毒完全灭活，同时保留病毒表面的保护性结构/表位，包括 完全维持血凝素(HA)活性。我们的初步数据显示，我们的第一次免疫小鼠- 通过皮下、经皮或鼻腔途径制备过氧化氢灭活疫苗 管理导致对致命流感的全面保护挑战。在这些拟议的研究中，我们描述了 我们的第二代AquVax平台技术以及我们将采取的进一步优化疫苗的方法 鼻腔接种疫苗后的效力。通过提高疫苗抗原的结构完整性，耦合 随着鼻腔给药途径的简便性和可接受性，我们希望提高这两种疫苗的效力 和疫苗接种覆盖面一起，将大大减少季节性流感对脆弱人群的影响 包括婴儿和老年人在内的人群。

Despite the development of several types of influenza vaccines (live-attenuated, inactivated, subunit), the World Health Organization estimates that seasonal influenza is still responsible for 3-5 million cases of severe disease and 290,000-650,000 deaths each year. Although vaccination programs have helped to reduce the morbidity and mortality associated with seasonal influenza, current vaccine approaches are limited by poor vaccine- mediated immunity and low vaccination coverage. To overcome suboptimal immune responses to influenza vaccination, we have developed an advanced hydrogen peroxide-based, site-directed oxidation technology that renders viruses fully inactivated while preserving protective structures/epitopes on the virus surface including fully maintained HA (hemagglutinin) activity. Our preliminary data shows that immunization of mice with our 1st- generation peroxide-inactivated vaccine by either the subcutaneous, transcutaneous, or intranasal routes of administration leads to full protection against lethal influenza challenge. In these proposed studies, we describe our 2nd-generation HydroVax platform technology and the approaches that we will take to further optimize vaccine potency following intranasal vaccination. By improving the structural integrity of the vaccine antigen, coupled with the ease and acceptability of an intranasal route of administration, we hope to improve both vaccine potency and vaccination coverage that together, will greatly reduce the impact of seasonal influenza among vulnerable populations including infants and the elderly.