Innovative peptide-loaded hybrid membrane nanovaccine enables precise personalized immunotherapy for HPV-related...

Human papillomavirus (HPV)-associated cervical diseases pose significant health risks to women worldwide. Current clinical interventions face challenges in achieving complete viral clearance and controlling disease progression, with limited efficacy and recurrence risks. To address this unmet need, we developed an innovative nanovaccine (HM-NPs@LP) designed to codeliver tumor cell membranes (TMs), bacterial cytoplasmic membranes (EMs), and HPV16 long peptides (LP) through PLGA nanoparticles to elicit antitumor immunity. HPV16 E5/E6/E7 LP and TM provide individualized broad-spectrum antigen repertoires, including tumor-specific and tumor-associated antigens. EMs serve as natural adjuvants to enhance immunogenicity. The resulting nanovaccine demonstrates uniform nanoparticles (177 nm) with excellent stability and biosafety. In vitro, HM-NPs@LP exhibited efficient uptake by bone marrow-derived dendritic cells (BMDCs), which in turn promoted DC maturation and strengthened tumor-specific T-cell responses. In vivo studies in murine models demonstrate that HM-NPs@LP preferentially accumulate in lymph nodes and elicit potent tumor suppression. Furthermore, this vaccination induces durable immune memory to prevent tumor recurrence with minimal systemic toxicity. Additionally, humanized HLA-A*02:01 transgenic mice mirror these therapeutic outcomes. Synergy with taxane-platinum (TP) chemotherapy and anti-PD-1 immunotherapy further augments tumor regression. Overall, the scalable production, biosafety, and adaptability for personalized immunotherapy position this nanovaccine platform as a promising therapeutic strategy for the treatment of HPV-related cervical diseases and potentially other malignancies.