ArticleFrontiers in microbiology2025
Enhancement of immunogenicity of SARS-CoV-2 spike protein expressed in
Article in Frontiers in microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
As an immunogenic non-toxic mutant of diphtheria toxin (DT), cross-reacting material 197 (CRM197) exhibits a significant immunogenicity-enhancing effect on various pathogenic vaccines. However, its application in vaccines against highly pathogenic pathogens remains underexplored. In this study, we incorporated CRM197 into a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, aiming to identify a molecular adjuvant capable of inducing broad-spectrum neutralizing antibodies and to develop a subunit vaccine with stronger cross-reactivity, improved safety, and greater accessibility. Our findings revealed that compared to non-fused SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) (designated sRBD), the fusion of CRM197 with the SARS-CoV-2 S protein RBD (termed CRM-RBD) elicited stronger humoral immunity, Th1-biased cellular immune responses, and reduced immune evasion against SARS-CoV-2 variants in mice. Furthermore, mice immunized with CRM-RBD exhibited significantly lower mortality and reduced pulmonary pathology upon viral challenge. These results demonstrate that CRM197 substantially enhances the immunogenicity of SARS-CoV-2 vaccines, positioning it as an ideal candidate protein for developing SARS-CoV-2 vaccines with broader cross-reactivity.
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