CRM197

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CRM197 is a safe, modified form of the diphtheria toxin used in many vaccines to boost the immune response to polysaccharides and small pieces (haptens) attached to it. By linking these sugars or haptens to CRM197, the body’s immune system learns to recognize the germs more effectively.

The toxin’s harmful activity is turned off by a single amino acid change at position 52 (glutamic acid is replaced by glycine). This detoxified protein still has many sites that can be used to attach sugars or peptides, which is helpful for making vaccines.

CRM197 is a single protein chain of 535 amino acids (about 58.4 kDa) that naturally forms two subunits linked by disulfide bonds. The gene for CRM197 has been inserted into Corynebacterium diphtheriae, but production yields are usually low, so researchers are making the protein in other bacteria.

Commercially, CRM197 is made by several companies, including Primrose Bio (PeliCRM197) using a specialized production platform, the Serum Institute of India (Pseudomonas fluorescens), and Fina Biosolutions (EcoCRM) in E. coli. Scarab Genomics also produces recombinant CRM197 in engineered E. coli.

CRM197 is used in approved vaccines such as Prevnar (pneumococcal) and Menveo (meningococcal). It was also used in HiB vaccines (Hibtiter, approved in 1990 but discontinued in 2007). More vaccines and many research programs are exploring CRM197 as a carrier and as a platform for delivering other therapeutic ideas.

Beyond vaccines, CRM197 is being studied for cancer therapies and drug delivery, because it can bind certain receptors on cancer cells and serve as a carrier for other therapeutic payloads. Researchers are also exploring CRM197-based fusion proteins and peptide vaccines for infectious diseases, cancer, and Alzheimer’s disease.

A historical note: CRM197 was discovered in the 1970s as a non-toxic diphtheria mutant that could enhance immunogenicity, and it helped drive the development of the first widely used conjugate vaccines like Prevnar.