Novel nanotechnology based oral influenza vaccines

目前使用针头注射的流感疫苗接种需要每年更新疫苗株， 给全世界的医护人员带来了巨大的负担。口服疫苗，这是一种非常方便和安全的 疫苗接种途径，可以提高预防粘膜感染的流感病毒。然而很 在胃的恶劣环境中稳定疫苗抗原并靶向它们是一个具有挑战性的问题 肠道的免疫系统。我们的初步研究提供了证据， 如果疫苗的免疫原性得到增强， 接种疫苗可产生保护性免疫力。在我们探索下一代疫苗的过程中， 一种新的纳米技术配方，我们建议将流感疫苗封装到稳定的小珠状中， 用于口服疫苗递送的含有微球和纳米球的颗粒。待检测的口服疫苗 包括目前获得许可的针对2009年大流行性流感病毒的灭活疫苗和活疫苗。 目标1的主要重点是用耐酸材料封装流感疫苗， 胃环境中的疫苗抗原和配体，策略性地将它们靶向肠道 派伊尔淋巴结和M细胞的免疫系统。在目标2中，我们将确定交叉保护的广度 使用2009年大流行的人H1N1分离株的有希望的流感口服候选疫苗的有效性 流感病毒，以及异源和异亚型流感毒株。此外，我们将 评价口服疫苗在雪貂中的有效性，雪貂是临床前试验的更相关动物模型 人类流感疫苗。预计改进的口服疫苗接种将提供针对 包括2009年H1N1流感病毒在内的毒株，这将对临床 应用和改善公共卫生。

Current influenza vaccination using needle injections requires annual updates of vaccine strains and imposes a tremendous burden on healthcare workers worldwide. Oral vaccination, which is a very convenient and safe route for vaccination, could improve the prevention of mucosal infection by influenza viruses. However, it is a challenging problem to stabilize the vaccine antigens in the harsh environment of stomach and to target them to the immune system of intestines. Our preliminary studies provide evidence that inactivated influenza vaccines can provide heterosubtypic cross protection if their immunogenicity is enhanced, and that oral vaccination can confer protective immunity. In our quest to advance to the next generation of vaccines using novel nanotechnology formulation, we propose to encapsulate influenza vaccines into stabilized small beadlike particles containing microspheres and nanospheres for oral vaccine delivery. Oral vaccines to be tested include the currently licensed forms of inactivated and live vaccines against the 2009 pandemic influenza virus. The main focus in aim 1 will be to encapsulate the influenza vaccines with an acid resistant material to stabilize vaccine antigens in the gastric environment, and the ligands, strategically targeting them to the intestinal immune system of Peyer¿s patches and M cells. In Aim 2, we will determine the breadth of cross protective efficacy with promising influenza oral vaccine candidates using the human H1N1 isolate of the 2009 pandemic influenza virus, and heterologous and heterosubtypic influenza strains in a mouse model. In addition, we will evaluate the efficacy of oral vaccination in ferrets, which is a more relevant animal model for testing pre-clinical influenza vaccines for humans. It is expected that improved oral vaccination will provide protection against the strains including the 2009 H1N1 influenza virus, which would have significant implications for clinical applications and for improving the public health.