A SARS-CoV-2 nanoparticle vaccine based on chemical conjugation of loxoribine and SpyCatcher/SpyTag.

SARS-CoV-2 is a particularly transmissible virus that renders the worldwide COVID-19 pandemic and global severe respiratory distress syndrome. Protein-based vaccines hold great advantages to build the herd immunity for their specificity, effectiveness, and safety. Receptor-binding domain (RBD) of SARS-CoV-2 is an appealing antigen for vaccine development. However, adjuvants and delivery system are necessitated to enhance the immunogenicity of RBD. In the present study, RBD was chemically conjugated with loxoribine and SpyCatcher/SpyTag, followed by assembly to form a nanoparticle vaccine. Loxoribine (a TLR7/8 agonist) acted as an adjuvant, and nanoparticles functioned as delivery system for the antigen and the adjuvant. The nanoparticle vaccine elicited high RBD-specific antibody titers, high neutralizing antibody titer, and strong ACE2-blocking activity. It stimulated high splenic levels of Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-5) in BALB/c mice. It promoted the splenocyte proliferation, enhanced the CD4 and CD8 T cell percentage and stimulated the maturation of dendritic cells. The vaccine did not render apparent toxicity to the organs of mice. Thus, the nanoparticle vaccine was of potential to act as a preliminarily safe and effective candidate against SARS-CoV-2.