A novel HBc-S230 protein chimeric VLPs induced robust immune responses against SARS-CoV-2

Here, we report that four functional fragments of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike protein including receptor binding motif (RBM), fusion peptide (FP), heptad repeat 1 (HR1) and heptad repeat 2 (HR2) were chosen to develop a recombinant S subunit protein vaccine. This recombinant protein consisting of S230 amino acids (aa) (S230) bound specifically to the antibody from COVID-19-patients serum, which showed very strong antigenicity. The S230 was then engineered to present on the surface of Hepatitis B core (HBc) virus-like particles (VLPs) to develop HBc-S230 chimeric VLPs vaccine. Both vaccines induced strong humoral and cellular immune responses in mice, however, HBc-S230 chimeric VLPs elicited significantly higher immunogenicity than the S230. HBc-S230 chimeric VLPs promoted to generate not only dramatically higher levels of S230-specific serum antibodies, but also marked higher CD4+/CD8 + T cells ratio and substantially higher yields of IFN-γ and IL-6. Furthermore, HBc-S230 chimeric VLPs induced serum antibodies that could effectively neutralize the infection with three SARS-CoV-2 pseudoviruses (Wild type, Delta and Omicron). Our results demonstrated that HBc-S230 chimeric VLPs immunization conveyed the humoral immunity, which lasted longer than six months. Clearly, HBc-S230 chimeric VLPs enhanced immunogenicity of the S230, which could provide potent and durable protection against SARS-CoV-2 infection, indicating that HBc-S230 chimeric VLPs possessed great potential for developing highly immunogenic vaccines against SARS-CoV-2.