Microneedles Based Thermally Stable Ad-5 Viral Vector for Vaccine Delivery

Cold chain dependence and inconvenient needle/syringe-based injections limit the global deployment of adenoviral (Ad) vectored vaccines, which play significant roles in veterinary vaccinology and offer an effective tool to protect humans against potential pandemics/endemics. Herein, a new Ad5-FMD vaccine stabilizing and delivery technology is presented, termed as Stabilized Prophylactic Adenovirus Nanostructure Delivery via Microneedles (SPAND-MN), which enables room-temperature storage and easy-to-use, painless transdermal administration of Ad vectored vaccines. It is demonstrated the success of SPAND-MN platform to deliver replication-defective Adenovirus serotype 5 (Ad5) vaccine vectors expressing various antigens, including Green Fluorescent Protein (GFP), Luciferase (Luc), and Foot-and-Mouth Disease (FMD) capsid proteins. The SPAND-MN formulation preserved transduction capacity of the Ad5 vaccines after exposure to an accelerated temperature (at 60°C) and a long-term storage at 45°C for 1 month. In vitro and in vivo studies confirmed effective transduction efficiency, dose delivery, and biocompatibility of the SPAND-MN platform. In vivo safety assessments revealed no cytotoxicity, systemic inflammation, and organ toxicity. SPAND-MNs maintained immunogenicity equivalent to injections of the stock refrigerated vaccines even after thermal challenges. These results demonstrate the potential of SPAND-MNs to offer a powerful, easy-to-use, cold-chain free, and painless transdermal skin patch for Ad5 vaccination.