Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine
优化通用流感亚单位纳米/微粒疫苗
基本信息
- 批准号:10540741
- 负责人:
- 金额:$ 56.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-15 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcetalsAcidsAddressAdjuvantAffectAgonistAlgorithmsAnimal ModelAnimalsAnthrax diseaseAntibody ResponseAntigen PresentationAntigensAntiviral AgentsAvian InfluenzaB-Cell ActivationBiopolymersBirdsCD4 Positive T LymphocytesCellsCessation of lifeConsensusCytosolDataDependenceDextransDoseDrug Delivery SystemsEmergency SituationEmulsionsEncapsulatedEndotoxinsEvaluationFDA approvedFerretsFormulationGenetic DriftGlycolatesGoalsHemagglutininHourHumanImmuneImmune responseIndividualInfectionInfection preventionInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A virusIntramuscularMethodologyModelingMusMutationNeuraminidaseNoseParticulatePathogenesisPathogenicityPathologyPeriodicityPhagocytesPhagosomesPlaguePolyestersPolymersPopulationProtein DenaturationProtein SubunitsRouteScheduleSeasonsShapesStimulator of Interferon GenesSubunit VaccinesSurfaceSystemTestingToxic effectVaccinatedVaccinationVaccinesViral Load resultVirus Diseasesaluminum sulfatecomputer generatedcontrolled releasecost effectivedesignfluhead-to-head comparisonimmunological synapseimmunoregulationimprovedinfluenza infectioninfluenza virus vaccineinfluenzavirusinnovationmouse modelnanonanoparticlenew pandemicnovelpandemic diseasepandemic influenzaparticlepreventprocess optimizationprotective efficacyreceptorresponsevaccine deliveryvaccine efficacyvaccine evaluationvaccine formulation
项目摘要
ABSTRACT
The WHO estimates there are approximately 5 million cases of influenza infections annually, with approximately
500,000 deaths occurring globally. The most cost-effective protection against influenza is vaccination.
Unfortunately, due to yearly antigenic shifts and drifts, current seasonal vaccines are ineffective. There is a need
for a better flu vaccine. In order to design a better flu vaccine, we plan on optimizing the immune synapse using
nano/microparticles (MPs) fabricated from the polymer acetalated dextran (Ac-DEX). Our previous data has
shown a dependence of particle degradation and optimal immune response against an influenza antigen. Not
only does the release of the antigen effect the immune response, the release of the adjuvant is also important.
The optimized degradation of both adjuvant and antigen has a drastic change in survival compared to non-
optimized formulations. Our particle system is unique because it relies on the highly tunable polymer Ac-DEX.
Ac-DEX is ideal for delivery of agents to phagocytic cells because it is acid-sensitive and has significantly
increased degradation in the low acid (~pH 5) of the phagosome. In addition to this it has tunable degradation
rates that can range from hours to months, which is a unique range from commonly used polyesters (e.g.
poly(lactic-co-glycolic acid) (PLGA)) that have degradation on the order of months. Moreover, Ac-DEX is unique
from polyesters because its degradation products are pH neutral, and do not have the potential to shift the local
pH or damage sensitive payloads. We have three specific aims exploring various optimizations of our particle
system. Aim 1 is focused on formulation of the polymer and particles. The release rate of the adjuvant will be
explored. Ac-DEX polymer with various cyclic acetal coverages will be fabricated to degrade over a broad range
of times. In Aim 2 we will evaluate the effect of loading of a novel influenza antigen either on the surface or
encapsulated into the MPs. We will explore degradation rates on antigen release as well as delivery routes in
determining the optimal delivery of influenza antigens that provide a broad range of protection. In Aim 3 we will
explore our optimized system in protecting ferrets. Ferrets are the ideal large animal model for influenza infection.
Using this model, we will evaluate the vaccine efficacy of our formulation, in comparison to a commercially
available flu vaccine.
摘要
世卫组织估计,每年约有500万例流感感染病例,
全球有50万人死亡。预防流感最具成本效益的方法是接种疫苗。
不幸的是,由于每年的抗原变化和漂移,目前的季节性疫苗是无效的。有必要
更好的流感疫苗为了设计出更好的流感疫苗,我们计划使用
由聚合物缩醛化葡聚糖(Ac-DEX)制造的纳米/微米颗粒(MP)。我们之前的数据显示
显示了颗粒降解和针对流感抗原的最佳免疫应答的依赖性。不
只有抗原的释放影响免疫应答,佐剂的释放也是重要的。
佐剂和抗原两者的优化降解与非优化降解相比在存活方面具有急剧变化。
优化配方。我们的粒子系统是独一无二的,因为它依赖于高度可调的聚合物Ac-DEX。
Ac-DEX对于将药剂递送至吞噬细胞是理想的,因为它是酸敏感的并且具有显著的细胞毒性。
在吞噬体的低酸(~pH 5)中的降解增加。除此之外,它还具有可调的降解能力,
速率的范围可以从数小时到数月,这是与常用聚酯(例如,
聚(乳酸-共-乙醇酸)(PLGA)),其具有数月量级的降解。此外,Ac-DEX是独一无二的
因为其降解产物是pH中性的,并且不具有改变局部
pH值或损伤敏感有效载荷。我们有三个具体的目标,探索我们的粒子的各种优化
系统目标1集中于聚合物和颗粒的配制。佐剂的释放速率将为
探讨了将制造具有各种环状缩醛覆盖率的Ac-DEX聚合物,以在宽范围内降解
的时代。在目的2中,我们将评估在表面或表面上负载新流感抗原的效果。
封装在MP中。我们将探索抗原释放的降解速率以及递送途径,
确定提供广泛保护的流感抗原的最佳递送。在目标3中,
探索我们保护雪貂的优化系统。雪貂是流感病毒感染的理想大型动物模型。
使用该模型,我们将评估我们的制剂的疫苗效力,与商业上的疫苗相比,
可用的流感疫苗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Kristy M Ainslie其他文献
Kristy M Ainslie的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Kristy M Ainslie', 18)}}的其他基金
Mechanistic evaluation of mast cell agonists combined with TLR, NOD and STING agonists.
肥大细胞激动剂联合 TLR、NOD 和 STING 激动剂的机制评估。
- 批准号:
10657847 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
- 批准号:
10449370 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Diversity Supplement - Formulation to Generate Tolerance Towards Type 1 Diabetes
多样性补充剂 - 产生对 1 型糖尿病耐受性的配方
- 批准号:
10560761 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
- 批准号:
10436981 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
- 批准号:
10713401 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
- 批准号:
10675073 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
- 批准号:
10310642 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Formulation to Generate Tolerance Towards Type 1 Diabetes
产生对 1 型糖尿病耐受性的配方
- 批准号:
10615119 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Tunable Temporal Drug Release for Optimized Synergistic Combination Therapy of Glioblastoma
可调节的时间药物释放,用于优化胶质母细胞瘤的协同联合治疗
- 批准号:
10309049 - 财政年份:2021
- 资助金额:
$ 56.04万 - 项目类别:
Optimizing a Universal Influenza Subunit Nano/Microparticulate Vaccine
优化通用流感亚单位纳米/微粒疫苗
- 批准号:
10328236 - 财政年份:2020
- 资助金额:
$ 56.04万 - 项目类别:
相似国自然基金
具有抗癌活性的天然产物金霉酸(Aureolic acids)全合成与选择性构建2-脱氧糖苷键
- 批准号:22007039
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
海洋放线菌来源聚酮类化合物Pteridic acids生物合成机制研究
- 批准号:
- 批准年份:2019
- 资助金额:10.0 万元
- 项目类别:省市级项目
手性Lewis Acids催化的分子内串联1,5-氢迁移/环合反应及其在构建结构多样性手性含氮杂环化合物中的应用
- 批准号:21372217
- 批准年份:2013
- 资助金额:80.0 万元
- 项目类别:面上项目
对空气稳定的新型的有机金属Lewis Acids催化剂制备、表征与应用研究
- 批准号:21172061
- 批准年份:2011
- 资助金额:30.0 万元
- 项目类别:面上项目
钛及含钛Lewis acids促臭氧/过氧化氢体系氧化性能的广普性、高效性及其机制
- 批准号:21176225
- 批准年份:2011
- 资助金额:60.0 万元
- 项目类别:面上项目
基于Zip Nucleic Acids引物对高度降解和低拷贝DNA检材的STR分型研究
- 批准号:81072511
- 批准年份:2010
- 资助金额:31.0 万元
- 项目类别:面上项目
海洋天然产物Makaluvic acids 的全合成及其对南海鱼虱存活的影响
- 批准号:30660215
- 批准年份:2006
- 资助金额:21.0 万元
- 项目类别:地区科学基金项目
相似海外基金
Lipid nanoparticle-mediated Inhalation delivery of anti-viral nucleic acids
脂质纳米颗粒介导的抗病毒核酸的吸入递送
- 批准号:
502577 - 财政年份:2024
- 资助金额:
$ 56.04万 - 项目类别:
CAREER: Highly Rapid and Sensitive Nanomechanoelectrical Detection of Nucleic Acids
职业:高度快速、灵敏的核酸纳米机电检测
- 批准号:
2338857 - 财政年份:2024
- 资助金额:
$ 56.04万 - 项目类别:
Continuing Grant
Double Incorporation of Non-Canonical Amino Acids in an Animal and its Application for Precise and Independent Optical Control of Two Target Genes
动物体内非规范氨基酸的双重掺入及其在两个靶基因精确独立光学控制中的应用
- 批准号:
BB/Y006380/1 - 财政年份:2024
- 资助金额:
$ 56.04万 - 项目类别:
Research Grant
Quantifying L-amino acids in Ryugu to constrain the source of L-amino acids in life on Earth
量化 Ryugu 中的 L-氨基酸以限制地球生命中 L-氨基酸的来源
- 批准号:
24K17112 - 财政年份:2024
- 资助金额:
$ 56.04万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Synthetic analogues based on metabolites of omega-3 fatty acids protect mitochondria in aging hearts
基于 omega-3 脂肪酸代谢物的合成类似物可保护衰老心脏中的线粒体
- 批准号:
477891 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Operating Grants
Metabolomic profiles of responders and non-responders to an omega-3 fatty acids supplementation.
对 omega-3 脂肪酸补充剂有反应和无反应者的代谢组学特征。
- 批准号:
495594 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Molecular recognition and enantioselective reaction of amino acids
氨基酸的分子识别和对映选择性反应
- 批准号:
23K04668 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrated understanding and manipulation of hypoxic cellular functions by artificial nucleic acids with hypoxia-accumulating properties
具有缺氧累积特性的人工核酸对缺氧细胞功能的综合理解和操纵
- 批准号:
23H02086 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Basic research toward therapeutic strategies for stress-induced chronic pain with non-natural amino acids
非天然氨基酸治疗应激性慢性疼痛策略的基础研究
- 批准号:
23K06918 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular mechanisms how arrestins that modulate localization of glucose transporters are phosphorylated in response to amino acids
调节葡萄糖转运蛋白定位的抑制蛋白如何响应氨基酸而被磷酸化的分子机制
- 批准号:
23K05758 - 财政年份:2023
- 资助金额:
$ 56.04万 - 项目类别:
Grant-in-Aid for Scientific Research (C)