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

Funding

Donghua University 2024 Cultivation Project of Discipline Innovation()