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

世纪的三次人类流感大流行在全世界造成数千万人死亡。过去数年，人类感染H5 N1禽流感病毒的个案时有发生，令科学界相信，H5 N1病毒与季节性流感病毒重组后，可能会出现一种强毒病毒，导致另一次大流行。疫苗是预防和干预流感大流行的关键工具，这一点已成为普遍共识。如《大流行性流感国家战略执行计划》所述，大流行性流感防备工作广泛侧重于流感疫苗的研制和公民的快速免疫接种。FluGen的复制缺陷型M2 SR减毒活疫苗候选物已在动物和体外模型中显示，相对于目前市售的疫苗，特别是老年人疫苗，它具有上级特性。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，但在小鼠和雪貂中减弱。该疫苗提供针对多种流感病毒株的保护，并且由于其基于细胞的生产方法，可以快速生产。该项目的关键交付成果是开发M2 SR疫苗的稳定液体制剂，该制剂目前储存在-80 ° C下，具有可用于鼻内产品的关键质量属性。我们将使用复制缺陷型流感疫苗进行制剂开发，该制剂将使用FDA批准的赋形剂，使用Arestat™稳定技术。Arestat™是一种专利配方技术，可设计出具有上级稳定性的新型生物制剂。该技术已在与主要制药公司合作的各种重组蛋白和其他生物制剂中得到验证。目的是开发一种允许疫苗在2-8°C下储存的制剂，并允许超出该温度范围的偏移。

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.