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）

• 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
• 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

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

项目摘要/摘要 每年估计有1,940万儿童未收到世界推荐的疫苗 卫生组织，导致150万疫苗可预防的死亡。1,2大多数不受欢迎的儿童 生活在低收入和中等收入国家，经常获得医疗保健的机会。2,3近600万 儿童至少接受一次疫苗剂量，但由于尚未完成全部剂量而保持危险 方案4,5一种疫苗接种方法，可在一次注射中输送所有剂量的疫苗或多种疫苗 即使是一次性获得医疗保健的儿童，可以完全保护相应的医疗保健 传染病。不幸的是，大多数受控药物输送系统表现出连续释放 动力学，与以多种离散剂量给药的传统可溶性疫苗有很大不同 几个月的课程。一项最近的一项研究描述了可生物降解的微粒平台的发展 封装疫苗的芯壳的聚合物壳，该芯芯在一段时间后表现出延迟的脉动释放 由聚合物降解速率确定。6 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，原始的微粒生产方法负面 影响抗原稳定性，需要使用大型针头，并且是低通量的。这个项目试图 通过使用同轴电喷雾（单步制造）制备微粒来克服这些挑战 可以产生单个水性，疫苗的芯子的过程，该核心被聚合物壳包围。父母 提案首先旨在创建带有密集的聚合壳的小核壳微粒，以证明 使用荧光标记的模型分子在体外和体内延迟的脉动释放大分子的脉动释放 和记者蛋白质以评估微粒内的蛋白质稳定性。这种多样性补充将扩大 以前建议支持Belvi Bwela的工作范围 在休斯顿社区学院，包括临床上的白喉毒素的封装和稳定 相关疫苗。在最初的工作范围中，该项目旨在封装辣根过氧化物酶和 溶血传感器黄色/蓝色标记的葡萄糖作为模型化合物，这些化合物易于通过 酶活性和比率荧光。在该奖项的扩大范围中，Belvi将稳定 在颗粒制造过程中，使用赋形剂和二乳酸（乳酸 - 乙醇酸）微粒中的二尖毒素毒素 体外释放。最终，这些颗粒可以作为与传染病作斗争的关键工具 在资源有限的发展中国家，在发达国家，没有保险的儿童和 农村社区始终显示较低的疫苗接种覆盖范围。7