Intranasal Delivery of HPV Therapeutic Vaccines for Enhanced Mucosal Immunization and Anti-Tumor Immunity.

Persistent infection with high-risk human papillomavirus (HPV) is widely acknowledged as the leading cause of cervical, oral, and other malignant cancers. Currently approved HPV vaccines are prophylactic and show no significant therapeutic effect on pre-existing infections or lesions. Considering the important role of mucosal vaccines in inducing localized immune responses against mucosal cancer, in this work, we developed salcaprozate-modified chitosan (SCS) for intranasal delivery of the HPV vaccine. We found that SCS can self-assemble with the E749-57 (RAHYNIVTF) and the immune adjuvant CpG to form nanoparticles, enabling penetration through the nasal mucosal barrier. This nanovaccine not only showed potent antitumor efficacy in subcutaneous tumor models but also induced stronger antigen-specific mucosal immune responses and systemic cellular immunity in oropharyngeal cancers and cervical cancer models, compared to traditional intramuscular injection. Therefore, our work presents a noninvasive carrier for effective intranasal delivery of nanovaccines, showing advantages in triggering more potent mucosal immunity while presenting enhanced patient compliance.