Research Supplement to Promote Diversity: Belvi Bwela (R03EB031495 Parent Award)

促进多样性的研究补充：Belvi Bwela（R03EB031495 家长奖）

基本信息

批准号：
10592142
负责人：
Kevin James McHugh
金额：
$ 1.5万
依托单位：
RICE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10592142
关键词：
Antigens Applications Grants Award Child Communicable Diseases Development Dextrans Diphtheria Toxoid Dose Drug Delivery Systems Electrospinning Encapsulated Enrollment Excipients Exhibits Fluorescence Glycolates Horseradish Peroxidase In Vitro Injections Kinetics Label Measures Methods Modeling Needles Parents Patients Physiologic pulse Polymers Population Process Production Property Proteins Regimen Reporter Research Resource-limited setting Resources Risk Rural Community Structure Time Toxoids Uninsured Vaccination Vaccines Work World Health Organization aqueous base black women clinically relevant community college controlled release fight against health care availability in vivo low and middle-income countries macromolecule negative affect parent grant particle preventable death ratiometric tool undergraduate student vaccination schedule

项目摘要

PROJECT SUMMARY/ABSTRACT Every year an estimated 19.4 million children do not receive the set of vaccines recommended by the World Health Organization, leading to 1.5 million vaccine-preventable deaths.1,2 A majority of undervaccinated children live in low- and middle-income countries and often have limited access to healthcare.2,3 Nearly 6 million of these children receive at least one vaccine dose, but remain at risk because they have not completed the full dosing regimen.4,5 A vaccination method that delivers all doses of a vaccine, or multiple vaccines, in a single injection would enable children with even one-time access to healthcare to be fully protected from the corresponding infectious disease. Unfortunately, most controlled-release drug delivery systems exhibit continuous release kinetics, which is vastly different from traditional soluble vaccines administered in multiple discrete doses over a course of months. One recent study has described the development of biodegradable microparticle platform with a polymer shell encapsulating a vaccine-loaded core that exhibits delayed, pulsatile release after a period determined by the polymer degradation rate.6 By injecting patients with a mixed population of particles with different degradation rates, vaccine can be released as discrete pulses, thereby mimicking traditional vaccination schedules known to be safe and effective. Unfortunately, the original microparticle production method negatively affects antigen stability, requires the use of large-gauge needles, and is low-throughput. This project seeks to overcome these challenges by preparing microparticles using coaxial electrospraying, a single-step fabrication process that can produce a single aqueous, vaccine-loaded core surrounded by a shell of polymer. The parent proposal first aims to create small core-shell microparticles with dense polymeric shells that demonstrate the delayed, pulsatile release of macromolecules in vitro and in vivo using fluorescently-labeled model molecules and reporter proteins to assess protein stability within the microparticles. This diversity supplement will expand the scope of work previously proposed to support the work of Belvi Bwela, a Black female undergraduate student at Houston Community College, including the encapsulation and stabilization of diphtheria toxoid, a clinically relevant vaccine. In the original scope of work, this project aimed to encapsulate horseradish peroxidase and LysoSensor Yellow/Blue-labeled dextran as model compounds which properties that are easy to measure via enzymatic activity and ratiometric fluorescence. In the expanded scope under this award, Belvi will stabilize diphteiria toxoid within poly(lactic-co-glycolic acid) microparticles using excipients during particle fabrication and in vitro release. Ultimately, these particles could serve as a key tool in the fight against infectious disease both in the developing world where resources are limited and in the developed world, where uninsured children and rural communities show consistently lower vaccination coverage.7

项目概要/摘要每年估计有 1940 万儿童没有接种世界推荐的疫苗卫生组织，导致 150 万人因疫苗可预防的死亡。1,2 大多数儿童未接种疫苗生活在低收入和中等收入国家，获得医疗保健的机会往往有限。2,3 其中近 600 万人儿童至少接受了一剂疫苗，但由于尚未完成全部剂量，因此仍面临风险方案 4,5 在单次注射中提供所有剂量的疫苗或多种疫苗的疫苗接种方法将使即使是一次性获得医疗保健的儿童也能得到充分保护，免受相应的影响传染病。不幸的是，大多数控释药物递送系统表现出连续释放动力学，这与传统的可溶性疫苗在一段时间内以多个离散剂量施用有很大不同几个月的过程。最近的一项研究描述了可生物降解微粒平台的开发聚合物外壳封装了负载疫苗的核心，在一段时间后表现出延迟的脉冲释放由聚合物降解率决定。6 通过向患者注射混合颗粒群不同的降解率，疫苗可以作为离散脉冲释放，从而模仿传统的疫苗接种已知安全有效的时间表。不幸的是，原来的微粒生产方法产生了负面影响影响抗原稳定性，需要使用大规格针头，且通量低。该项目旨在通过使用同轴电喷雾（一步制造）制备微粒来克服这些挑战该过程可以产生一个由聚合物壳包围的单一水性、负载疫苗的核心。家长该提案的第一个目标是创建具有致密聚合物壳的小核壳微粒，以证明使用荧光标记的模型分子在体外和体内延迟、脉动释放大分子和报告蛋白以评估微粒内的蛋白质稳定性。这种多样性补充将扩大之前提出的支持黑人女本科生 Belvi Bwela 工作的工作范围在休斯顿社区学院，包括白喉类毒素的封装和稳定化，白喉类毒素是一种临床相关疫苗。在最初的工作范围内，该项目旨在封装辣根过氧化物酶和 LysoSensor 黄色/蓝色标记的葡聚糖作为模型化合物，其特性易于通过以下方式测量酶活性和比率荧光。在该奖项扩大的范围内，贝尔维将稳定在颗粒制造过程中使用赋形剂将白喉类毒素置于聚（乳酸-乙醇酸）微粒中，体外释放。最终，这些颗粒可以作为对抗传染病的关键工具在资源有限的发展中国家和没有保险的儿童和农村社区的疫苗接种覆盖率始终较低。7