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

项目总结/摘要 每年估计有1940万儿童没有得到世界卫生组织推荐的疫苗。 世界卫生组织，导致150万可通过疫苗预防的死亡。1，2大多数儿童疫苗接种不足 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。 儿童至少接种了一剂疫苗，但由于没有完成全部接种， 方案4，5一种疫苗接种方法，在单次注射中递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也能得到充分保护， 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，这与在一个周期内以多个离散剂量施用的传统可溶性疫苗有很大不同。 几个月的过程。最近的一项研究描述了生物可降解微粒平台的发展， 一种聚合物壳，包封一个装载疫苗的核心，在一段时间后表现出延迟的脉冲式释放， 通过聚合物降解速率确定。6通过向患者注射混合颗粒群， 不同的降解速率，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，原始微粒生产方法不利地 影响抗原稳定性，需要使用大规格针，并且是低通量的。本项目谋求 通过使用同轴电喷雾制备微粒克服了这些挑战， 该方法可以产生被聚合物壳包围的单一含水的装载疫苗的核。母 该提案首先旨在产生具有致密聚合物壳的小核-壳微粒， 使用荧光标记的模型分子在体外和体内延迟、脉冲释放大分子 和报告蛋白来评估微粒内的蛋白质稳定性。这种多样性补充将扩大 先前提出的支持黑人女大学生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，临床上 相关疫苗在最初的工作范围内，该项目旨在包封辣根过氧化物酶， LysoSensor黄/蓝标记的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。在此奖项下扩大的范围内，Belvi将稳定 在颗粒制造过程中使用赋形剂在聚（乳酸-共-乙醇酸）微粒内制备白喉类毒素， 体外释放。最终，这些粒子可以作为对抗传染病的关键工具， 在资源有限的发展中世界和没有保险的儿童和 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