A Single‐Administration Microneedle Skin Patch for Multi‐Burst Release of Vaccine against SARS‐CoV‐2
Khanh T. M. Tran, Tyler D. Gavitt, Thinh T. Le, Adam Graichen, Feng Lin, Yang Liu, E. R. Tulman, Steven M. Szczepanek, Thanh D. Nguyen
Abstract
The necessity for multiple injections and cold-chain storage has contributed to suboptimal vaccine utilization, especially in pandemic situations. Thermally-stable and single-administration vaccines hold a great potential to revolutionize the global immunization process. Here, a new approach to thermally stabilize protein-based antigens is presented and a new high-throughput antigen-loading process is devised to create a single-administration, pulsatile-release microneedle (MN) patch which can deliver a recombinant SARS-CoV-2 S1-RBD protein-a model for the COVID-19 vaccine. Nearly 100% of the protein antigen could be stabilized at temperatures up to 100 °C for at least 1 h and at an average human body temperature (37 °C) for up to 4 months. Arrays of the stabilized S1-RBD formulations can be loaded into the MN shells via a single-alignment assembly step. The fabricated MNs are administered at a single time into the skin of rats and induce antibody response which could neutralize authentic SARS-CoV-2 viruses, providing similar immunogenic effect to that induced by multiple bolus injections of the same antigen stored in conventional cold-chain conditions. The MN system presented herein could offer the key solution to global immunization campaigns by avoiding low patient compliance, the requirement for cold-chain storage, and the need for multiple booster injections.