LAUSR

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.