Stabilization of Influenza Vaccine by Silica-Coating

二氧化硅涂层稳定流感疫苗

• 批准号: 9199795
• 负责人: James R Laidler
• 金额: $ 22.5万
• 依托单位: STONESTABLE, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9199795
• 关键词: Aftercare; Applications Grants; Attenuated; Attenuated Live Virus Vaccine; Binding; Biological Assay; Child; Clinical Treatment; Cold Chains; Desiccation; Disease; Electron Microscopy; Enzyme-Linked Immunosorbent Assay; Failure; Freezing; Goals; Heating; Hemagglutination; Immune response; Immunity; In Vitro; Incubated; Life; Logistics; MDCK cell; Manufacturer Name; Modeling; Mus; Phase; Plaque Assay; Process; Recovery; Refrigeration; Research; Shipping; Ships; Silicon Dioxide; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Suspension substance; Suspensions; T-Lymphocyte; Techniques; Technology; Temperature; Testing; Time; Toxicity Tests; Transmission Electron Microscopy; Vaccines; Vaccinia virus; Virion; Virus; Work; cell mediated immune response; extreme temperature; immunogenicity; in vivo; influenza virus vaccine; liquid formulation; mouse model; novel; reconstitution; vaccine candidate

The goal of this Phase I STTR grant proposal is to stabilize live attenuated influenza vaccine (LAIV) using a temporary silica coating that is removed in vivo. In so doing, we will establish a broader technology to eliminate the cold-chain required for transport of heat and cold labile vaccines. Many vaccines are unstable under ambient environmental conditions. Currently vaccines are either stabilized in liquid formulations and must be kept between 2-8C, or are lyophilized, stored frozen, and then reconstituted just before use. Maintaining the cold chain demands great expense and logistic issues for distribution, with the result that an estimated 1.5 million children die each year worldwide from vaccine-preventable diseases. We have developed a proprietary technology to reversibly inactivate a wide variety of viruses by coating them with silica. The coating confers the viruses with extraordinary tolerance to dessication. This coating is completely reversible and dissolves in vivo, rendering the viruses once again effective as vaccines; in a preliminary test, both silica-coated and uncoated vaccinia virus induced similar T-cell mediated immune responses in vivo in a murine model. We hypothesize that we can silica-coat live attenuated influenza vaccine and that this coating will stabilize the vaccine suspension at ambient temperatures, eliminating the need for refrigeration or freezing. To establish proof of concept, we propose three aims in Phase I: Aim 1. Coat and uncoat LAIV with silica. Aim 2. Show that coated LAIV is stabilized in vitro. Aim 3. Show that coated LAIV replicates and generates an immune response in vivo. At the conclusion of this Phase I STTR project, we will have reached our Milestones: showing that we can coat LAIV and the coating protects the vaccine from inactivation yet still causes an immune response. Thereby we will have established proof-of-concept for silica coating of vaccines without loss of immunogenicity, and will be poised to launch Phase II, in which we will work directly with vaccine manufacturers and developers to stabilize their vaccines and vaccine candidates, develop industrial- scale coating processes, show that coated vaccines confer protective immunity, and perform toxicity testing to support regulatory filing.

这项第一阶段STTR拨款提案的目标是使用一种稳定的减毒活流感疫苗（LAIV）， 在体内去除的临时二氧化硅涂层。这样做，我们将建立一个更广泛的技术，以消除 运输冷热不稳定疫苗所需的冷链。许多疫苗在接种后不稳定。 周围环境条件。目前，疫苗要么在液体制剂中稳定， 保持在2- 8 ℃之间，或者冻干，冷冻储存，然后在临用前重构。维持 冷链需要很大的费用和物流问题的分配，其结果是，估计1.5 全世界每年有100万儿童死于疫苗可预防的疾病。我们开发了一种专有的 通过用二氧化硅包被病毒来可逆地包裹各种病毒的技术。涂层赋予 这些病毒对干燥有着非凡的耐受性。这种涂层是完全可逆的， 体内，使病毒再次有效的疫苗;在初步测试中，二氧化硅涂层和 未包被的牛痘病毒在鼠模型中体内诱导类似的T细胞介导的免疫应答。我们 假设我们可以用二氧化硅包被减毒活流感疫苗，并且这种包被将稳定 在环境温度下悬浮疫苗，无需冷藏或冷冻。建立 为了验证概念，我们在第一阶段提出了三个目标：目标1。用二氧化硅涂覆和去除LAIV涂层。目标二。显示 包被的LAIV在体外是稳定的目标3.表明包被LAIV复制并产生免疫 体内反应。在第一阶段STTR项目结束时，我们将达到我们的目标： 这表明我们可以给LAIV涂上一层涂层，这种涂层可以保护疫苗不被灭活， 免疫反应因此，我们将建立疫苗二氧化硅涂层的概念验证 而不损失免疫原性，并将准备启动第二阶段，在这一阶段，我们将直接与 疫苗生产商和开发商稳定他们的疫苗和候选疫苗，开发工业- 规模涂层工艺，表明涂层疫苗赋予保护性免疫力，并进行毒性试验， 支持监管备案。

项目成果

Comparative genetic and genomic analysis of the novel fusellovirus Sulfolobus spindle-shaped virus 10.

• DOI: 10.1093/ve/vey022
• 发表时间: 2018-07
• 期刊: Virus evolution
• 影响因子: 5.3
• 作者: Goodman DA;Stedman KM
• 通讯作者: Stedman KM