Besides effectiveness, how to induce long-term protective efficacy remains a major challenge in contemporary vaccine development. The commonly used aluminum adjuvants stimulate TH2 immunity and activate humoral immune responses, but are limited in stimulating TH1 and CD8+T cell immunity. Despite its widespread use, there is still no unified and clear conclusion on the mechanism of aluminum adjuvants. Therefore, the development of new vaccine with long-term protective effects is of great significance.
Recently, Signal Transmission and Targeted Therapy published a paper of Prof. CHEN Chunying’s group from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS), entitled "Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine". This paper evaluated the immune persistence and related mechanisms of the COVID subunit vaccine with manganese nanoadjuvant (MnARK).
“Compared with traditional adjuvants, the precisely designed nanoadjuvants can enhance lymph node (LN) targeting and increase antigen-presenting cell (APCs) uptake, achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses” says CHEN Chunying, a Professor of NCNST and the lead author of the current work. On the basis of previous work, the research team from NCNST led by Prof. CHEN Chunying explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 receptor-binding domain (RBD) dimer antigen. MnARK-adjuvanted SARS-CoV-2 subunit vaccines induced high levels of RBD-specific antibody responses over 360 days. Encouragingly, at day 360, MnARK group maintained (neutralizing antibody) NAb titers at GMT of 512, 3 times than that of alum group. Compared with alum, MnARK particularly promoted antigen uptake by B cells, enhanced the formation of germinal centers, and the proportion of germinal center B cells.
To further investigate the features of MnARK-induced immunity, we performed mass cytometry (CyTOF) analysis of CD45+ cells in muscles and lymph nodes isolated from mice in the MnARK vaccinated group and the unvaccinated control group. It was found that after immunization with MnARK, immune cells including DC and B cells were rapidly recruited in the muscle, promoting the expression of major histocompatibility complex II (MHC II) and thus promoting antigen presentation. Within lymph nodes, MnARK activated memory lymphocytes, including memory T cells and helper T cells, and promoted the maturation of B cells.
“MnARK promoted antigen presentation by targeting lymph nodes. Furthermore, MnARK activated B cells, promoted the production of memory cells and germinal centers, thereby inducing long-term immune memory and providing new ideas for the development of immune persistence vaccines” says Professor CHEN Chunying.
Fig.1 Durable humoral and cellular immune responses induced by MnARK-based subunit vaccine. (Image by CHEN Chunying et al)
Contact:
CHEN Chunying
National Center for Nanoscience and Technology (NCNST)
