Besides optimizing the antigen, incorporating a suitable adjuvant into the subunit vaccine is one potential strategy to improve the weak RBD immunogenicity, decrease the number of vaccinations and antigen dosage, and also induce potent neutralizing antibodies as well as cell-mediated immune responses.
Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) has been committed to the immune regulation performance of inorganic nanoparticles (ACS Nano 2020, 14 (5), 5529-5542; ACS Nano 2020, 14 (11), 15700-15713.), mainly focused on the precise assembly and efficient delivery of the protein subunit vaccines and nucleic acid vaccines. Additionally, Prof. Chen established and developed analytical methods for nanomaterials in complex biological systems based on synchrotron radiation and other large scientific facilities. (Nature Nanotechnol., 2019, 14, 639; Acc. Chem. Res., 2019, 52, 1507; JACS, 2021, 143, 1846; JACS, 2013, 135, 17359 etc.).
In situ, non-destructive analysis has great significance for understanding the behavior of nanoadjuvants in antigen-presenting cells, clearly elucidating the immune regulation mechanism, and precisely constructing new vaccine nanoadjuvants. The advantages of these methods are high sensitivity, high resolution, element specificity, in situ, etc.. These advanced methods will provide key and cutting-edge analytical techniques for nano-biological effects and nano-medicine research, and provide important evaluation methods for promoting the clinical transformation of bio-products such as nano-biomedicine and vaccines.
Recently, Prof. Chen, 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. This work was published in Nano Today.
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 (Nat. Nanotechnol. 2021. DOI: 10.1038/s41565-021; Acc. Chem. Res. 2019, 52 (6), 1507-1518.). Exploiting the characteristics of albumin as a transporter and biotemplate, researchers proposed an antigen-adjuvant-formulated nanovaccine, composed of the RBD antigen of the S protein and the manganese nanoadjuvant (MnARK). Herein, the negatively charged cubic manganese oxide nanoparticle was designed to activate the cGAS-STING pathway and transport RBD antigens to LNs via electrostatic-driven self-assembly. Meanwhile, the FITC-tagged nanovaccine was imaged through both confocal and synchrotron radiation hard X-ray nano-CT, to observe the RBD and three-dimensional distribution of MnARK in DCs.
It is confirmed that RBD antigen and manganese nanoadjuvant can be efficiently co-delivered to lymph nodes. simultaneously promoting the uptake of antigen-presenting cells, and stimulating 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, 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.
This work was financially supported by the Program for International S&T Cooperation Projects of the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science, the National Basic Research Program of China, Strategic Priority Research Program of the Chinese Academy of Sciences, the Research and Development Project in Key Areas of Guangdong Province, the National Natural Science Foundation of China and the Beijing Synchrotron Radiation Light Source, etc. .
Figure 1: Design of antigen/MnARK adjuvant co-delivered nanovaccine to combat novel coronavirus.