Ultra-low dose Influenza vaccines

7.项目摘要/摘要 目前的季节性流感疫苗被证明是无效的，特别是在有风险的 人口。例如，今年的灭活流感疫苗只有9%的有效率 预防老年人感染H3N2病毒和目前的流感减毒活疫苗 (LAIV)年龄限制为49岁以上的人。因此，有一个明显的 未满足的需求--有效的季节性流感疫苗。 石溪大学开发的翻译型疫苗平台技术 名为SAVE(合成减毒病毒工程)的研究在 在实验室菌株A/波多黎各/8/34中产生抗甲型流感疫苗，即 在非常低的剂量下对动物有效。这个Shift奖旨在改变这一点 通过应用节约，将学术发现带入商业产品的开端 技术，以季节性相关的人类菌株，然后比较疗效与 当前的LAIV。优势的展示将增加该公司的商业可行性 技术以及满足当前未得到满足的医疗需求-流感疫苗具有高 在所有人群中都有疗效。目前流感疫苗的缺点是双重的--两者 灭活注射疫苗或目前的LAIV需要大量病毒 每剂量颗粒物&gt；107，和2)在老年人群中的疗效都很低。这个 SAVE技术可以为这两个限制提供解决方案。 SAVE平台依赖于合成生物学和目标病毒的“重新设计” 以产生疫苗毒株。此定制过程使用软件- 基于算法对目标病毒的基因组进行重新编码。基因组“重新编码”的结果 在抗原性相同的病毒中(即看起来与野生型毒力完全相同) 菌株)，但拥有一个带有数百个突变的基因组，使其在 主持人。由于SAVE设计的疫苗毒株的蛋白质为100 与强毒株完全相同，动物接种了SAVE设计的疫苗 疫苗产生一种强大的保护性免疫反应。储蓄是一个平台 已初步成功构建候选疫苗的技术 多种无关的目标病毒，包括脊髓灰质炎病毒和甲型流感病毒(科学 2008、自然生物技术2010)。 在这项提议的第一阶段，我们将应用SAVE技术来构建疫苗 临床上相关的季节性流感病毒株的候选者，随后 我们将把这些毒株与目前商用的减毒活流感进行比较。 展示商业可行性的疫苗。在第二阶段，我们将在成功的基础上再接再厉 并在雪貂模型中测试我们节省设计的季节性流感候选疫苗。

7. Project Summary/Abstract Current seasonal Influenza vaccines are proving to be ineffective, especially in at risk populations. For example, this year's inactivated flu vaccine had only a 9% efficacy rate against H3N2 infections in the elderly and the current live-attenuated Influenza vaccine (LAIV) is aged restricted for those above 49 years of age. Therefore there is glaring unmet need - seasonal Influenza vaccines that are effective. A translational, vaccine platform technology developed at Stony Brook University entitled SAVE (Synthetic Attenuated Virus Engineering) has shown initial success in yielding an anti-Influenza A vaccine in the laboratory strain A/Puerto Rico/8/34 that is effective in animals at very low doses. This SHIFT award seeks to transform this academic discovery into the beginnings of commercial product, by applying the SAVE technology to seasonally relevant human strains and then compare efficacy against the current LAIV. Demonstration of superiority will increase the commercial viability of the technology as well as fulfill a current unmet medical need - flu vaccines that have high efficacy in all populations. The drawbacks of current flu vaccines are two-fold- 1) both the inactivated injectable vaccine or the current LAIV require a large quantity of viral particles per dose >107, and 2) both have low efficacy in the aged population. The SAVE technology could provide a solution to both of these limitations. The SAVE platform relies on synthetic biology and the "re-designing" of a target virus's entire genome to yield a vaccine strain. This customization process uses software- based algorithms to 're-code' the genome of a target virus. Genomic 're-coding' results in a virus that is antigenically identical (i.e. looks exactly like the wild-type, virulent strain) but possesses a genome with hundreds of mutations rendering it attenuated in the host. Since proteins of the SAVE-designed vaccine strain are one hundred percent identical to the virulent strain, animals vaccinated with SAVE-designed vaccines develop a robust and protective immune response. SAVE is a platform technology that has had preliminary success constructing vaccine candidates for multiple, unrelated target viruses including poliovirus and Influenza a virus (Science 2008, Nature Biotech 2010). In Phase I of this proposal we will apply the SAVE technology to construct vaccine candidates for seasonal influenza strains that are clinically relevant and subsequently we will compare these strains to the current commercial live-attenuated influenza vaccine to demonstrate commercial viability. In Phase II we will build upon our success and test our SAVE-designed seasonal influenza vaccine candidates in a ferret model.