Research Supplement to Promote Diversity: Carlos Torres (R03EB031495 Parent Award)

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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 Carlos Torres, a Hispanic male undergraduate student at Houston Community College, including the investigation of coaxial electrospraying parameters between pieces of electrospraying equipment. The goal of Carlos’s work is to identify the key features that affect core-shell microparticle morphology and release kinetics and develop solutions that allows electrospraying conditions to be readily transferred between different pieces of equipment. If successful, Carlos’s work will enhance the reproducibility of science and allow different research groups to work in unison to improve electrosprayed particle formulations for single-injection vaccination as well as other drug delivery applications. 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