Sequential Immunization with Vaccines Based on SARS-CoV-2 Virus-like Particles Induces Broadly Neutralizing Antibodies

Although many people have been vaccinated against COVID-19, infections with SARS-CoV-2 seem hard to avoid. There is a need to develop more effective vaccines and immunization strategies against emerging variants of infectious diseases. To understand whether different immunization strategies using variants sequence-based virus-like particles (VLPs) vaccines could offer superior immunity against future SARS-CoV-2 variants, our team constructed VLPs for the original Wuhan-Hu-1 strain (prototype), Delta (δ) variant, and Omicron (ο) variant of SARS-CoV-2, using baculovirus-insect expression system. Then we used these VLPs to assess the immune responses induced by homologous prime-boost, heterologous prime-boost, and sequential immunizations strategies in a mouse model. Our results showed that the pro+δ+ο sequential strategies elicited better neutralizing antibody responses. These sequential strategies also take advantage of inducing CD4⁺ T and CD8⁺ T lymphocytes proliferation and tendency to cytokine of Th1. Currently, our data suggest that sequential immunization with VLPs of encoding spike protein derived from SARS-CoV-2 variants of concern may be a potential vaccine strategy against emerging diseases, such as "Disease X".