An Antigen/STING Agonist Conjugation-Based Nanovaccine with Responsive Release Promoting Dendritic Cell Maturation

Abstract

To develop a nanovaccine capable of synchronously delivering antigens and adjuvants for effective dendritic cell(DC)maturation, we covalently conjugated the stimulator of interferon gene(STING)agonist MSA-2 with the model antigen CSIINFEKL via a cleavable linker. The resulting prodrug was co-assembled with phosphoethanolamine-polyethylene glycol(DSPE-PEG)to form a nanovaccine(termed NV_AA). The NV_AA exhibited a uniform spherical morphology with an average hydrodynamic diameter of approximately 20 nm and a zeta potential of - 14 mV. Upon internalization by DCs, the covalently conjugated antigen and STING agonist enabled their synchronized intracellular delivery, leading to efficient activation of the STING signaling pathway. As a result, NV_AA significantly enhanced the secretion of IFN-β, IL-6, and IL-12, and upregulated the expression of costimulatory molecules CD80 and CD86 on DCs. These findings demonstrate that the covalent conjugation-based nanovaccine NV_AA effectively promotes DC maturation via STING pathway activation, providing a promising strategy for cancer immunotherapy.

Keywords

nanovaccine / reduction-responsive release / STING pathway / dendritic cell maturation / immunotherapy

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Funding

Donghua University 2024 Cultivation Project of Discipline Innovation, China