There is also evidence suggesting that, compared with tetanus toxoid, there is less carrier-induced suppression of the immune response, especially when there are many individual polysaccharides linked to the same carrier protein.

The low yield and high cost of commercially available native CRM197 has led to efforts to produce CRM197 in other bacteria but this has proven a difficult task until recently.

Fina BioSolutions LLC of Rockville, Maryland has achieved multi-gram/L expression of CRM197 in E. coli (“EcoCRMTM”) as an intracellular, properly folded soluble protein.

Recombinant CRM197 is also made in low-mutation Clean Genome® E. coli by Scarab Genomics LLC where transport of CRM197 into the bacterial cell periplasm enhances its stability and proper folding.

[6] Preclinical studies have shown that CRM197 is also suitable for conjugation and presentation of peptide epitopes, a vaccinal approach that could have applications in Streptococcal infection,[11] cancer,[12] or Alzheimer's disease[13] therapy.

In 1971 Tsuyoshi Uchida, in the laboratory of Alwin Pappenheimer at Harvard, used nitroguanidine to create mutants of diphtheria toxin, which were called Cross Reacting Materials, or CRMs.

[15] The pharmaceutical company Wyeth took advantage of this immunogenicity in the 1990s when it conjugated seven polysaccharides from Streptococcus pneumoniae to CRM197 to create the original Prevnar vaccine which was FDA approved in February 2000.