Developing Stable Liquid Pandemic Influenza Vaccines to Improve Shelf Life, Facilitate Distribution, and Increase Pandemic Preparedness

20世纪的3次人类流感大流行导致全球数千万人死亡。过去几年，人类零星感染H5N1禽流感病毒，使科学界认为，H5N1病毒和季节性流感病毒重新分类后，可能会出现一种毒力强的病毒，导致另一场大流行。人们普遍认为，疫苗是预防和干预流感大流行的关键工具。如《国家大流行性流感战略执行计划》所述，大流行性流感防备工作广泛侧重于建立流感疫苗和公民的快速免疫接种。FluGen的复制缺陷M2SR减毒活疫苗候选疫苗在动物和体外模型中表明，相对于目前市场上销售的疫苗，它具有更好的性能，特别是在老年人中。FluGen的研究表明，缺乏部分基因组的流感病毒在细胞培养中复制良好，但在小鼠和雪貂身上会减弱。由于其基于细胞的生产方法，这种疫苗能够对多种流感病毒株提供保护，并可以快速生产。该项目的关键成果是开发稳定的M2SR疫苗液体制剂，目前储存在-80°C，其关键质量属性可用于鼻腔产品。我们将使用复制缺陷流感疫苗进行配方开发，该疫苗将使用美国食品和药物管理局批准的辅料，使用Arest at™稳定技术。ARSTAT™是一种专有配方技术，可用于设计具有卓越稳定性的新型生物制剂液体配方。这项技术已经在与主要制药公司合作的一系列重组蛋白质和其他生物制品上得到了验证。其目的是开发一种配方，允许疫苗在2-8摄氏度下储存，并允许超出这一温度范围的短途旅行。

The 3 human influenza pandemics in the 20th century killed tens of millions of people worldwide. Sporadic human infections by avian H5N1 virus in the past few years have led the scientific community to believe that a virulent virus may emerge as the result of re-assortment between H5N1 virus and seasonal influenza virus, causing another pandemic. There is universal consensus that vaccines are a key tool to prevent and intervene in an influenza pandemic. Pandemic influenza preparedness, as detailed in the Implementation Plan for the National Strategy for Pandemic Influenza, focuses extensively on the establishment of influenza vaccines and on the rapid immunization of citizens. FluGen’s replication deficient M2SR live attenuated vaccine candidate has shown in animal and in vitro models that it has superior properties relative to currently marketed vaccines particularly in the elderly. FluGen’s studies have demonstrated that influenza viruses lacking a portion of their genome replicate well in cell culture but are attenuated in mice and ferrets. This vaccine confers protection against multiple strains of Influenza and can be rapidly produced, due to its cell based production method. The key deliverable of this project is to develop stable liquid formulation of the M2SR vaccine, which is currently stored at -80°C, with critical quality attributes acceptable for use in intranasal products. We will use the replication deficient Flu vaccine for formulation development, which will use FDA approved excipients, using Arestat™ stabilisation technologies. Arestat™ is a proprietary formulation technologyallowing the design of novel liquid formulations of biologics with superior stability. Thetechnology has been validated on a wide range of recombinant proteins and other biologics in collaboration with major pharma companies. The aim is to develop a formulation that allows for storage of the vaccine at 2-8°C with allowances for excursions outside of this temperature range.