Poria cocos polysaccharide-honeycomb manganese oxide nanoparticles adjuvant enhanced immune responses to PCV2 vaccine via TLR4-mediated NF-κB activation enhanced STING pathway.

Adjuvants, as indispensable ingredients in vaccines, possess the capability to enhance the magnitude, breadth, and durability of immune responses. Traditional alum adjuvants principally elicit a potent humoral immune response, yet demonstrate an inability to effectively stimulate a cellular immune response. We previously successfully prepared the Poria cocos polysaccharide-honeycomb manganese oxide nanoparticles (PMn) system, and the PMn has the capability to facilitate the activation of dendritic cells (DCs) and enhance immune responses. Herein, we further investigated the underlying mechanisms of DCs activation, and explored the potential adjuvant activity of the PMn for the porcine circovirus type 2 (PCV2) vaccine. It was found that the PMn promoted the DCs activation via both TLR4-NF-κB and cGAS-STING activation. And the TLR4-mediated NF-κB activation could enhance the STING activation. Furthermore, the PMn, as the adjuvant for the PCV2 vaccine, promoted the activation of DCs and the induction of germinal center in lymph nodes, stimulated vigorous humoral and cellular immune responses, inducing robust and balanced antibody production and stimulating effective antigen-specific T cell response. Collectively, the PMn adjuvant may provide valuable insights for the development of the polysaccharide- and manganese-based nanoparticles adjuvant capable of eliciting both innate and adaptive immune responses, with potential applications in human and veterinary vaccines.