Diphtheria cross-reacting material 197 protein (CRM197)

Diphtheria cross-reacting material 197 protein (abbreviated CRM197) is a genetically detoxified mutant of diphtheria toxin, featuring a single amino acid substitution (Gly52 to Glu; G52E) that abolishes its ADP-ribosyltransferase activity, thereby rendering it nontoxic. CRM197 retains the overall structure and immunogenicity of diphtheria toxin but does not cause disease. It is widely used as a carrier protein in polysaccharide-protein conjugate vaccines to enhance immunogenicity, enabling effective vaccination against encapsulated bacteria such as *Haemophilus influenzae*, *Streptococcus pneumoniae*, and *Neisseria meningitidis*. Structurally, CRM197 is a single-chain holoprotein with two main domains corresponding to fragments A (catalytic domain, inactivated) and B (transmembrane domain), linked by disulfide bridges. The protein is highly characterized, with crystal structures available, and demonstrates residual deoxyribonuclease activity, but is unable to ADP-ribosylate elongation factor 2, eliminating its cytotoxic potential. Its nontoxic nature and robust immunogenicity make CRM197 a standard carrier protein in licensed conjugate vaccines for global childhood immunization programs.

Other names

CRM197Cross-reacting material 197CRM 197Diphtheria toxin mutant G52E

Increases immunogenicity of polysaccharide antigens through T-cell dependent immune response by acting as a carrier protein in conjugate vaccines