In a study published in Nano Today, Prof. CHEN Chunying from the National Center for Nanoscience and Technology of the Chinese Academy of Sciences, collaborating with LIU Ye from the Institute of Medical Biology, Chinese Academy of Medical Sciences, reported a new type of manganese nanoadjuvant formulated SARS-CoV-2 subunit vaccine. They proposed a "tri-in-one" nano-vaccine strategy by integrating protein in situ adjuvant mineralization and antigen co-delivery, multi-scale vaccine tracking, and omics analysis of immune mechanism. 

Albumin is the most ubiquitous protein in blood and interstitial fluid, which affects the transport, metabolism, and bioavailability of nanomaterials in vivo when forming protein corona. Exploiting the characteristics of albumin as a transporter and biotemplate, the researchers proposed an antigen-adjuvant-formulated nanovaccine, composed of the RBD antigen of the S protein and the manganese nanoadjuvant (MnARK).  

They designed the negatively charged cubic manganese oxide nanoparticle to activate the cGAS-STING pathway and transport RBD antigens to LNs via electrostatic-driven self-assembly. Meanwhile, they imaged the FITC-tagged nanovaccine through both confocal and synchrotron radiation hard X-ray nano-CT, to observe the RBD and three-dimensional distribution of MnARK in DCs.  

The results showed that RBD antigen and manganese nanoadjuvant can be efficiently co-delivered to lymph nodes, which simultaneously promotes the uptake of antigen-presenting cells, and stimulates cellular as well as humoral immune responses.  

Compared with the manganese ion vaccine, the MnARK nanovaccine has significantly improved safety and immune stimulation. Notably, even at a 5-fold lower antigen dose and with fewer injections, the MnARK vaccine immunized mice showed stronger neutralizing abilities against the infection of the pseudovirus (~270-fold) and live coronavirus (>8-fold) in vitro than that of Alum-adsorbed RBD vaccine (Alu-RBD).  

Furthermore, the researchers found that the effective co-delivery of RBD antigen and MnARK to lymph nodes (LNs) elicited an increased cellular internalization and the activation of immune cells, including DCs, CD4⁺ and CD8⁺ T lymphocytes, and can stimulate the production of memory T cells, resulting in long-term antigen-independent maintenance. 

Prof. CHEN has been committed to the study of immune regulation performance of inorganic nanoparticles mainly on the precise assembly and efficient delivery of the protein subunit vaccines and nucleic acid vaccines.