A SARS-CoV-2 vaccine based on conjugation of SARS-CoV-2 RBD with IC28 peptide and mannan

SARS-CoV-2 is a particularly transmissible virus that causes a severe respiratory disease known as COVID-19. Safe and effective vaccines are urgently needed to combat the COVID-19 pandemic. The receptor-binding domain (RBD) of SARS-CoV-2 spike protein elicits most neutralizing antibodies during viral infection and is an ideal antigen for vaccine development. In particular, RBD expressed by E. coli is amenable to low cost and high-yield manufacturability. The adjuvant is necessitated to improve the immunogenicity of RBD. IC28, a TLR5-dependent adjuvant, is a peptide from bacterial flagellin. Mannan is a ligand of TLR-4 or TLR-2 and a polysaccharide adjuvant. Here, IC28 and mannan were both covalently conjugated with RBD from E. coli. The conjugate (RBD-IC28-M) elicited high RBD-specific IgG titers, and a neutralization antibody titer of 201.4. It induced high levels of Th1-type cytokines (IFN-γ) and Th2-type cytokines (IL-5 and IL-10), along with high antigenicity and no apparent toxicity to the organs. The mouse sera of the RBD-IC28-M group competitively interfered with the interaction of RBD and ACE2. Thus, conjugation with IC28 and mannan additively enhanced the humoral and cellular immunity. Our study was expected to provide the feasibility to develop an affordable, easily scalable, effective vaccine SARS-CoV-2 vaccine.