Multifunctional Polymer-Modified P-CaO2@Au@OVA@Cu@DHPs Nanoparticles Enhance SARS-CoV-2 mRNA Vaccine-Induced Immunity via the cGAS-STING Signaling Pathway.

The success of mRNA-based SARS-CoV-2 vaccines has been confirmed in both preclinical and clinical settings. However, the development of safe and efficient mRNA vaccine delivery platforms remains challenging. In this report, PBAE-G-B-SS-modified CaO2 nanofibers and Au@OVA@Cu@Dendrobium huoshanense polysaccharides were employed to establish novel self-assembling polymeric micelles (CaO2@Au@OVA@Cu@DHPs) capable of serving as both an adjuvant and a delivery system for mRNA vaccines. In vitro, CaO2@Au@OVA@Cu@DHPs nanoparticles (NPs) were conducive to effective macrophage antigen uptake and efficient antigen processing. In vivo, P-CaO2@Au@OVA@Cu@DHPs NP administration was associated with a reduction in the ovalbumin (OVA) release rate that was conducive to the sustained induction of long-term immunity and to the production of higher levels of different IgG subtypes, suggesting that these effects were attributable to enhanced antigen uptake by antigen-presenting cells. Overall, these present data highlight the promise of these P-CaO2@Au@OVA@Cu@DHPs NPs as an effective and safe platform amenable to vaccine delivery through their ability to provide robust adjuvant activity and sustained antigen release capable of eliciting long-term immunological memory while potentiating humoral and cellular immune responses.