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Materials Development for Transdermal Vaccination 1. Motivation Vaccines currently represent a significant strategy for the control of infectious disease on a global level. However, despite the successes of modern vaccine development, there remain several notable obstacles for the advancement of vaccine-mediated improvements in global healthcare. Among these are factors which limit vaccine availability, such as cost and the need for cold storage, or vaccine efficacy and compliance, such as the ease and speed of vaccine delivery. Many of the current limitations in vaccine availability and administration are the result of obligate needle-based delivery, which in addition to contributing to reduced speed, ease, and compliance in administration, has been shown to contribute to reduced overall safety due to needle re-use and needle-based injuries. The inherent limitations of needle-based vaccination on global health, together with emerging concern over global pandemic disease, has led to a strong impetus to develop needle-free vaccination strategies which have the potential to improve vaccine availability, enhance the ease, speed, and safety of vaccine administration, and reduce vaccination-associated costs world-wide. Thus, the development of needle-free vaccination platforms has been identified by the World Health Organization and the Centers for Disease Control and Prevention as a major research priority in the improvement of global health. 2. Development of Polyelectrolyte Films for Transdermal Vaccination Vaccination through transcutaneous delivery of antigen/adjuvant represents a promising strategy for inducing protective immunity. For example, the abundance of Langerhans cells, resident epidermal antigen-presenting-dendritic-cells, has been shown to mediate both systemic and mucosal immunity through antigen uptake, presentation, and subsequent activation of the adaptive immune response. Therefore, transcutaneous delivery may produce a more robust immune response relative to traditional intramuscular injection which only elicits systemic immunity. In addition, transcutaneous delivery platforms may provide opportunities for solid state vaccine stabilization precluding the need for “cold chain” support, and improving overall global availability. Unlike needle-based delivery, transcutaneous delivery platforms may also allow for robust dosage control for multiple antigen/adjuvant species and discrete time resolved release allowing for more effective immune activation. This should improve vaccine effectiveness and overall patient compliance. Finally, transcutaneous vaccine delivery provides improvements associated with the needle-free administration paradigm, including increased safety, improved speed and ease of administration, and reduced training requirements for health care providers. The central goal of my proposed work is the development of vaccination platforms using polyelectrolyte films for the controlled encapsulation and transcutaneous delivery of antigen/adjuvant combinations. Specifically, I hope to develop strategies for film construction that will 1) allow for the incorporation of a variety of antigen and adjuvant species 2) provide for solid state vaccine stabilization resistant to environmental fluctuation and 3) allow for defined and tunable multi-component antigen and adjuvant release. To this end, layer-by-layer (LbL) polyelectrolyte adsorption has been shown to be a promising method for the construction of thin films with nanoscale compositional control translating to fine temporal control of release. LbL polyelectrolyte film construction is also well suited for encapsulation of biologically active species due to mild aqueous adsorption conditions. Variables defining film composition and degradation offer a large experimental space for system optimization, and additional control may be introduced through the use of films incorporating hydrolytic polymer conjugates or macroscopic carriers such as nanoparticles and micelles. Finally, the optimization of physical substrates for film deposition such as micro-needles may further enhance potential systems. I expect to explore this variable space to develop robust platforms for transcutaneous vaccine delivery and characterize these platforms for efficacy in producing protective immunity.
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