Hepatitis B vaccination using a dissolvable microneedle patch

Abstract

Despite improved vaccination rates against hepatitis B, there remain critical barriers to addressing gaps in vaccination coverage. The need of an effective supply chain, vaccine waste management, trained healthcare providers and cost are all issues that impede mass vaccination campaigns around the world. Microneedle patches have been proposed as an alternative mode of vaccination. Microneedle patches consist of micron-scale projections that are capable of disrupting the stratum corneum by creating holes in the skin to deliver therapeutic agents. Small and lightweight, microneedle patches are a promising alternative to the bulky multi-dose vials and syringes currently used in mass vaccination campaigns. Furthermore, the high density of antigen presenting cells in the the skin make transcutaneous immunization via microneedles advantageous, as they target vaccine cargo to the topmost layer of the skin. The key goal of this project was to develop a microneedle patch for hepatitis B vaccination that is simple to administer and of comparable immunogenicity to conventional intramuscular vaccination. Trehalose was used as a stabilizing excipient for both coated metal and dissolvable microneedles. Moreover, patches were used in vivo to compare the elicited immune response in both mice and rhesus macaques. Additionally, the mechanical properties of our microneedle patch were evaluated via both theoretical and experimental approaches to predict failure force. This work shows that microneedle patches can successfully encapsulate and deliver hepatitis B antigen to generate a strong and sustained immune response in multiple animal models.