ABSTRACT
Protein subunit vaccines have been widely used to combat infectious diseases, including the current COVID-19 pandemic. Adjuvants play the key role in shaping the quality and magnitude of the immune response to protein and inactivated vaccines. We previously developed a protein subunit COVID-19 vaccine, termed ZF2001, based on an aluminium hydroxide-adjuvanted tandem-repeat dimeric receptor-binding domain (RBD) of the viral spike (S) protein. Here, we described the use of a squalene-based oil-in-water adjuvant, Sepivac SWE™ (abbreviated to SWE), to further improve the immunogenicity of this RBD-dimer-based subunit vaccines. Compared with ZF2001, SWE adjuvant enhanced the antibody and CD4+ T-cell responses in mice with at least 10 fold of dose sparing compared with ZF2001 adjuvanted with aluminium hydroxide. SWE-adjuvanted vaccine protected mice against SARS-CoV-2 challenge. To ensure adequate protection against the currently circulating Omicron variant, we evaluated this adjuvant in combination with Delta-Omicron chimeric RBD-dimer. SWE significantly increased antibody responses compared with aluminium hydroxide adjuvant and afforded greater neutralization breadth. These data highlight the advantage of emulsion-based adjuvants to elevate the protective immune response of protein subunit COVID-19 vaccines.
Subject(s)
COVID-19 Vaccines , Adjuvants, Vaccine , Protein Multimerization , Antibodies, Viral/immunology , SARS-CoV-2/genetics , Mutation , Mice, Inbred BALB C , Humans , Animals , Mice , Binding Sites , Cell LineABSTRACT
The SARS-CoV-2 Omicron variants of concern (VOCs) showed severe resistance to the early-approved COVID-19 vaccines-induced immune responses. The breakthrough infections by the Omicron VOCs are currently the major challenge for pandemic control. Therefore, booster vaccination is crucial to enhance immune responses and protective efficacy. Previously, we developed a protein subunit COVID-19 vaccine ZF2001, based on the immunogen of receptor-binding domain (RBD) homodimer, which was approved in China and other countries. To adapt SARS-CoV-2 variants, we further developed chimeric Delta-Omicron BA.1 RBD-dimer immunogen which induced broad immune responses against SARS-CoV-2 variants. In this study, we tested the boosting effect of this chimeric RBD-dimer vaccine in mice after priming with two doses of inactivated vaccines, compared with a booster of inactivated vaccine or ZF2001. The results demonstrated that boosting with bivalent Delta-Omicron BA.1 vaccine greatly promoted the neutralizing activity of the sera to all tested SARS-CoV-2 variants. Therefore, the Delta-Omicron chimeric RBD-dimer vaccine is a feasible booster for those with prior vaccination of COVID-19 inactivated vaccines.