Ultra-low dose Influenza vaccines

超低剂量流感疫苗

• 批准号: 8853806
• 负责人: Steffen Mueller
• 金额: $ 19.99万
• 依托单位: CODAGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8853806
• 关键词: Age-Years; Algorithms; Animal Model; Animals; Apple; Attenuated; Attenuated Live Virus Vaccine; Attenuated Vaccines; Award; Biotechnology; California; Centers for Disease Control and Prevention (U.S.); Code; Computer Assisted; Computer software; Development; Dose; Elderly; Engineering; FDA approved; Ferrets; Flushield; Generations; Genes; Genetic; Genome; Genomics; Glare; Goals; Head; Human; Human poliovirus; Immune response; Inbred BALB C Mice; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A virus; Injectable; Laboratories; Leadership; Life; Marketing; Medical; Methods; Modeling; Mus; Mutation; Names; Nature; Phase; Polioviruses; Population; Populations at Risk; Preclinical Testing; Process; Puerto Rico; Research; Science; Seasons; Small Business Innovation Research Grant; Solutions; System; Technology; Testing; Time; Universities; Vaccinated; Vaccines; Viral; Virulence; Virulent; Virus; Work; aged; anti-influenza; base; clinically relevant; comparative efficacy; design; design and construction; engineering design; head-to-head comparison; influenza virus vaccine; influenzavirus; manufacturing process; novel; pandemic disease; particle; pre-clinical; preclinical efficacy; protective efficacy; public health relevance; research clinical testing; research study; seasonal influenza; success; synthetic biology; synthetic protein; vaccine candidate; vaccine development

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.

7. 项目总结/摘要 目前的季节性流感疫苗被证明是无效的，尤其是在高风险地区 人口。例如，今年的灭活流感疫苗有效率只有9% 预防老年人 H3N2 感染和当前的减毒活流感疫苗 (LAIV) 年龄限制为 49 岁以上。因此有刺眼的 未满足的需求 - 有效的季节性流感疫苗。 石溪大学开发的转化疫苗平台技术 题为SAVE（合成减毒病毒工程）的研究已取得初步成功 在实验室毒株 A/Puerto Rico/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。该 SHIFT 奖旨在改变这一现状 通过应用 SAVE，将学术发现转化为商业产品的开端 技术对季节性相关的人类菌株进行比较，然后与 目前的 LAIV。展示优势将提高商业活力 技术并满足当前未满足的医疗需求 - 流感疫苗具有高 对所有人群均有效。当前流感疫苗有两个缺点 - 1) 灭活注射疫苗或当前的 LAIV 需要大量病毒 每剂颗粒数 >107，和 2) 对老年人群的疗效均较低。这 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” 整个基因组以产生疫苗株。这个定制过程使用软件- 基于算法来“重新编码”目标病毒的基因组。基因组“重新编码”结果 在抗原相同的病毒中（即看起来与野生型、强毒力完全相同） 菌株），但其基因组有数百个突变，使其在 主人。由于SAVE设计的疫苗株的蛋白质有一百种 接种 SAVE 设计疫苗的动物与强毒株相同的百分比 疫苗会产生强大的保护性免疫反应。 SAVE是一个平台 已在构建候选疫苗方面取得初步成功的技术 多种不相关的目标病毒，包括脊髓灰质炎病毒和流感病毒（科学 2008 年，《自然生物技术》2010 年）。 在该提案的第一阶段，我们将应用SAVE技术来构建疫苗 具有临床相关性的季节性流感毒株候选者 我们将把这些毒株与目前商业化的减毒活流感病毒进行比较 疫苗以证明商业可行性。在第二阶段，我们将在我们的成功基础上再接再厉 并在雪貂模型中测试我们由 SAVE 设计的候选季节性流感疫苗。

项目成果

Live-attenuated H1N1 influenza vaccine candidate displays potent efficacy in mice and ferrets.

候选 H1N1 流感减毒活疫苗在小鼠和雪貂中显示出强大的功效。

• 发表时间: 2019
• 影响因子: 3.7
• 作者: Stauft, Charles B;Yang, Chen;Coleman, J Robert;Boltz, David;Chin, Chiahsuan;Kushnir, Anna;Mueller, Steffen
• 通讯作者: Mueller, Steffen