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

项目摘要/摘要 每年估计有1940万儿童没有接种世界卫生组织推荐的疫苗 卫生组织，导致150万可预防的疫苗死亡。1，2大多数未接种疫苗的儿童 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 儿童至少接种一剂疫苗，但仍有风险，因为他们没有完成全部剂量 方案4、5一次注射所有剂量的疫苗或多种疫苗的接种方法 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，使其免受相应的 传染病。不幸的是，大多数控释给药系统表现出持续释放。 Kinetics，这与传统的可溶性疫苗在一年内以多个离散剂量接种有很大不同 当然是几个月了。最近的一项研究描述了生物可降解微粒平台的发展 一种包裹疫苗装载核心的聚合物外壳，在一段时间后表现出延迟的脉冲式释放 由聚合物降解率确定。6通过给患者注射混合颗粒群体 不同的降解率，疫苗可以作为离散的脉冲释放，从而模仿传统的疫苗接种 已知的安全有效的时间表。不幸的是，最初的微粒生产方法是负面的 影响抗原稳定性，需要使用大口径针头，而且产量低。这一项目旨在 通过使用同轴电喷射法(一步法)制备微粒来克服这些挑战 这一过程可以产生一个由聚合物外壳包裹的单一水基疫苗核心。父辈 提议首先旨在创造具有致密聚合物外壳的小核壳微粒，以展示 利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 和报告蛋白来评估微粒内的蛋白质稳定性。这一多样性补充将扩大 之前为支持黑人女本科生Belvi Bwell a的工作而提议的工作范围 在休斯顿社区学院，包括白喉类毒素的封装和稳定，一种临床上 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/蓝标记葡聚糖作为模型化合物，其性质易于通过 酶活性和比率荧光。在这项裁决的扩大范围内，Belvi将稳定下来 聚乳酸-乙醇酸共聚微粒中的白喉类毒素在微粒制造和制备过程中使用辅料 体外释放。最终，这些颗粒可能会成为对抗传染病的关键工具 在资源有限的发展中国家和发达国家，没有保险的儿童和 农村社区的疫苗接种率一直较低。

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