Antigens and adjuvants co-stabilized Pickering emulsions amplify immune responses of subunit vaccines

Most subunit antigens often induce suboptimal vaccination efficacy, possibly due to their low immunogenicity and limited ability to migrate to lymph nodes (LNs). Although the emergence of nanovaccine has significantly addressed these challenges, most formulations still require specific biological or chemical modifications to the carrier or antigen for efficient antigen loading. In this study, we report a Pickering emulsion-based nanovaccine that directly utilized antigens and adjuvants as stabilizers, effectively amplifying immune responses without additional physicochemical alterations. In detail, the model antigen ovalbumin (OVA) and manganese particles mineralized with human serum albumin (HSA-Mn) synergistically functioned as stabilizers, while squalene served as the oily core, resulting in the nanoemulsion (OVA/HSA-MnNE) with a remarkable antigen encapsulation efficiency exceeding 90 %. The engineered OVA/HSA-MnNE significantly improved cellular internalization and maturation of dendritic cells. After subcutaneous vaccination, OVA/HSA-MnNE rapidly migrated into the LNs, substantially promoted endogenous 2′3´-cGAMP production, and further activated the cGAS-STING pathway, consequently eliciting valid cellular immune responses as well as 87.5 % preventive efficacy against EG7-OVA tumor. In sum, this study proposed the concept of utilizing antigens and adjuvants themselves as stabilizers of Pickering emulsions to construct nanovaccine, providing new insights for the future design of subunit vaccines. Visualization of the construction of Pickering emulsion-based nanovaccine and its utilization in lymph nodes (LN) targeting, efficient activation of the cGAS-STING pathway, and stimulation of adaptive immune responses. (a) The biomineralized Mn particles (HSA-Mn) serving as solid emulsifiers can stabilize the oil phase (squalene) with small antigen OVA to obtain the nano-emulsion vaccine OVA/HSA-MnNE. (b) After subcutaneous inoculation, OVA/HSA-MnNE rapidly migrates into draining lymph nodes, greatly promotes antigen cross-presentation efficacy and potently activates the cGAS-STING pathway and induces effective adaptive immune responses. (c) The detailed process of cGAS-STING pathway activation. [Display omitted]