ABSTRACT
The spike trimer of SARS-CoV-2 is an effective target for inducing neutralizing antibodies by COVID-19 vaccines. However, the diversity of spike protein from emerging SASR-CoV-2 variants has become the major challenge for development of a universal vaccine. In order to investigate the immunogenicity of spike proteins from various circulating strains including wild-type, Delta and Omicron variants, we produced various natural spike trimers and designed three vaccination strategies, i.e. individual, sequential and bivalent regimens to assess autologous and heterogenous antibody responses in a mouse model. The results indicated that monovalent vaccine strategy with individual spike trimer could only induce binding and neutralizing antibodies against homologous viruses. However, sequential and bivalent immunization with Delta and Omicron spike trimers could induce significantly broader neutralizing antibody responses against heterogenous SARS-CoV-2. Interestingl y, the spike trimer from Omicron variant showed superior immunogenicity in inducing antibody response against recently emerging XE variant. Taken together, our data supported the development of novel vaccination strategies or multivalent vaccine against emerging variants.
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