Self-amplifying mRNA nanovaccine encoding GM-CSF-fused HPV16 E7 enhances immunogenicity and therapeutic efficacy against cervical cancer
Cervical cancer, driven by the malignant transformation of keratinocytes via the human papillomavirus (HPV) E7 oncoprotein, remains a significant global health challenge. In this study, we developed an alphavirus-based self-amplifying mRNA (saRNA) vaccine encoding either a genetically engineered HPV16 E7 gene or a fusion of granulocyte-macrophage colony-stimulating factor (GM-CSF) with HPV16 E7, both encapsulated in self-assembling liposome-protamine-RNA (LPR) nanoparticles. SaRNA represents a promising vaccine platform due to its intrinsic ability to amplify and prolong antigen expression, offering a substantial advantage over conventional mRNA approaches. Intramuscular administration of LPR-saRNA-GM-CSF-E7 in mice triggered robust innate immune responses and activated antigen-presenting cells in the draining lymph nodes, leading to enhanced T-cell effector functions. The LPR-saRNA-GM-CSF-E7 nanovaccine more effectively reprogrammed the tumor microenvironment by reducing immunosuppressive cell populations and increasing Th1 cytokine expression compared to LPR-saRNA-E7. Importantly, in vivo cytotoxic T lymphocyte (CTL) assays demonstrated that LPR-saRNA-GM-CSF-E7 vaccination elicited potent E7-specific CD8
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Funding
Basic and Applied Basic Research Foundation of Guangdong Province Grant 2024A1515012277National Key Research and Development Program of China Stem Cell and Translational Research Grant 2023YFF0724202National Key Research and Development Program of China FundingNational Natural Science Foundation of China Grant 82172080