Enhancement of immunogenicity of SARS-CoV-2 spike protein expressed in Escherichia coli by fusion of the CRM197 functional domain

Enhancement of immunogenicity of SARS-CoV-2 spike protein expressed in Escherichia coli by fusion of the CRM197 functional domain

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 i...

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Main Authors: Xibing Yu, Yinmeng Yang, Miao Zhang, Qiantong Shen, Yun Zhu, Tong An, Siqi Li, Kexin Zhang, Shuaiyao Lu, Shaohong Lu, Fangcheng Zhuang, Meng Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Microbiology
Subjects:
CRM197
SARS-CoV-2
S protein
RBD
vaccines
adjuvant
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1650239/full
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Summary: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.
ISSN:1664-302X

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