목적: Despite the success of HPV vaccines in reducing cervical cancer and head and neck cancers in high-income countries through both female and male vaccination programs, implementation remains challenging in low- and middle-income countries. Key barriers include high costs, healthcare worker shortages, and vaccine stability issues. Traditional microneedle vaccine production methods often compromise virus-like particle (VLP) structural integrity, limiting vaccine effectiveness. 방법:We developed an optimized dissolving microneedle array patch incorporating HPV VLPs through a novel fabrication process. Stability assessments were conducted using scanning electron microscopy and dynamic light scattering over six months. Immune responses were evaluated in mice following buccal administration, with analysis of antigen trafficking, cellular responses, and antibody production. Long- term immunity was assessed through memory B cell and plasma cell quantification in various tissues, complemented by buccal and vaginal viral challenge studies. 결과:The engineered platform maintained VLP structural stability beyond six months. Buccal delivery effectively transported antigens to draining lymph nodes, promoting T follicular helper cell differentiation and robust germinal center formation. This resulted in high-titer neutralizing antibodies and cross-protective sterile immunity in both buccal and vaginal tissues. Memory immune responses persisted for six months, evidenced by stable populations of memory B cells and plasma cells in buccal tissue and bone marrow, conferring protection against viral challenges. 결론:Our dissolving microneedle platform addresses critical vaccination barriers in resource-limited settings by enhancing VLP stability and accessibility. The demonstration of durable cross-mucosal protection through buccal administration represents a significant advancement in HPV vaccination strategy. This technology's potential application to other structurally sensitive VLP-based vaccines positions it as a promising solution for global immunization challenges.