Identification of cyclophilin A as an effective and safe mucosal vaccine adjuvant for nasal vaccination 3405

Abstract Description The lack of clinically applicable mucosal adjuvants is a major hurdle in designing effective mucosal vaccines. Through a combination of bioinformatics and experimental validation approaches, we developed a nasal vaccine formulation by exploiting the adjuvant activity of cyclophilin A, a human damage-associated molecular pattern (DAMP) molecule. Intranasal immunization with the spike protein of SARS-CoV-2 adjuvanted by recombinant cyclophilin A elicited potent antigen-specific antibody responses and pulmonary cytotoxic T cell responses. Vaccination-mediated humoral and cellular immune responses were remarkably sustained for over six months in mice. Furthermore, the efficacy of cyclophilin A-mediated nasal vaccination was confirmed in rabbits, which possess a nasal structure similar to that of humans. As part of a mechanistic study, we demonstrated that cyclophilin A-pulsed dendritic cells potently activated cognate T cells. Furthermore, cyclophilin A exhibited comparable or even superior mucosal adjuvant activity to cholera toxin, which is considered the gold standard mucosal adjuvant in experimental models. Importantly, after nasal delivery, cyclophilin A did not induce inflammation in the olfactory bulb, in contrast to the unavoidable olfactory bulb inflammation induced by bacterial toxin-derived adjuvants, such as cholera toxin. In conclusion, cyclophilin A holds great promise as a robust adjuvant for the development of mucosal vaccines in clinical practice. Funding Sources Health and Medical Research Fund (Reference: 20190332) Topic Categories Vaccines and Immunotherapy (VAC)