Evaluation of humoral immune responses induced by different SARS-CoV-2 spike trimers from wild-type and emerging variants with individual, sequential, and combinational delivered strategies

The spike trimer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective target for inducing neutralizing antibodies by coronavirus disease 2019 (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. 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, that is, 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. Interestingly, 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.