A SARS-CoV-2 mucosal nanovaccine based on assembly of maltodextrin, STING agonist and polyethyleneimine.

SARS-CoV-2 has the characteristics of strong transmission with severe morbidity and mortality. Protein-based vaccines have the properties of specificity, effectiveness and safety against SARS-CoV-2. Receptor-binding domain (RBD) homotrimer affords high protection efficacy against stringent lethal viral challenge. Mucosal immunity could block the infection that first infect and replicate in the upper airway mucosa. Due to the physical barriers of the mucosa, mucosal vaccines necessitated appropriate adjuvants and delivery system. In the present study, maltodextrin, PEI and 2',3'-cGAMP acted as the mucosal adjuvants and RBD trimer as the antigen. A mucosal nanovaccine was prepared by assembly of adjuvants and the antigen to a nanoparticle. The vaccine elicited strong serum RBD-specific IgG and IgA response, and mild mucosal IgA and IgG response in the respiratory tract. It stimulated strong neutralizing antibody response and high ACE2-blocking activity in the sera. It promoted the RBD-specific CD4 and CD8 T cells secreting IFN-γ, IL-4 and IL-17 A. Moreover, it elicited durable RBD-specific memory T and B memory cell response, activated the T and B cells, enhanced the cytotoxic T cell killing effect, and promoted the maturation of DCs. These findings suggested the clinical potential of the vaccine to combat against SARS-CoV-2 infection.