Dissolving Microneedle for Maintaining the Integrity of HPV Virus-Like Particles Enabling Durable Sterile Protection Across Various Mucosal Tissues.

Human papillomavirus (HPV) vaccines have substantially reduced cervical cancer and other HPV-related diseases in high-income countries, with male vaccination addressing transmission as well as head and neck cancers. However, in low- and middle-income countries, widespread vaccination efforts are hindered by considerable costs, insufficient medical staff, and challenges in maintaining vaccine stability. Conventional microneedle vaccine production often compromises the structural integrity of virus-like particles (VLPs), thereby reducing their effectiveness. To address this challenge, a dissolving microneedle platform is developed that preserves VLP stability for over six months. Administration of this vaccine platform to buccal tissue enables effective antigen delivery, inducing T follicular helper (Tfh) cell differentiation, germinal center formation, and the production of high-titer neutralizing antibodies. Buccal application also conferred sterilizing immunity in both buccal and vaginal tissues. Moreover, the vaccine induced durable immune memory, with memory B cells and plasma cells persisting in buccal tissue and bone marrow for six months. This innovation addresses critical barriers in resource-limited regions by enhancing VLP stability and accessibility. Furthermore, the platform's applicability extends to other vaccines requiring structural integrity for efficacy, representing a transformative approach to global immunization efforts.