CRM197 carrier protein is a nontoxic mutant of diphtheria toxin; CRM197 has drawn considerable interest in the biotechnology industry, especially in conjugate Vaccines. This carrier protein has been found to be instrumental in boosting immunity to polysaccharide antigens that are nevertheless weakly immunogenic on their own. By linking these antigens to CRM197, vaccine developers are able to improve the quality of the produced vaccines, especially for various bacterial diseases such as Hib, Neisseria meningitidis, and Streptococcus pneumoniae. The properties, uses and rationale behind developing it, all are key areas that warrant a deserved devotion if one is to fully understand the value of this reagent in the contemporary world of biotechnology.
What is CRM197?
CRM197 is an altered native diphtheria toxin generated by the bacterium Corynebacterium diphtheriae. The native diphtheria toxin has high toxicity; the ADP-ribosylating activity it presents kills cells by inhibiting protein synthesis. However, analysis of the amino acid sequence of CRM197 revealed that this protein has a number of differences – it has a single amino acid substitution at position 52 with glycine converted to glutamic acid. This genetically alters CRM197 and makes it nontoxic to human but retains its strong antigenicity making it ideal for use in human vaccines.
Role of Carrier Proteins in Vaccines
Most bacterial CRM196 vaccines require a robust immune response to bacterial polysaccharides, which are a component of the bacterial cell wall, in order for them to be effective. These immunogens are T cell-responsive polysaccharides, which do not effectively invoke a prolonged immune response, especially in infants and most children.
When these polysaccharides are linked to a protein carrier like CRM197, the immune system recognizes them as T-cell-dependent antigens and, therefore, provides a better and longer-term immune response. Its effectiveness in this role is attributed to the GOP portion dependency; CRM197 mobilizes T-helper cells, resulting in antibodies produced against polysaccharides.
Chance in Conjugate Vaccines
The most common use of CRM197 has been found in conjugate vaccines. Some key vaccines utilizing CRM197 include:
Pneumococcal Conjugate Vaccines (PCVs): The bacteria can lead to severe illnesses like pneumonia, meningitis, and sepsis. CRM197 is employed in many PCVs to fix with pneumococcal polysaccharides, increasing the efficiency of the vaccine for multiple serotypes.
Meningococcal Vaccines: Neisseria meningitidis the bacteria that causes meningitis disease is another potential indication for CRM197 vaccines. This is achieved by linking the meningococcal polysaccharides to a carrier protein known as CRM197 and when added to vaccines they stimulate enhanced immune reactions giving a shield against various serogroups of the bacterium.
Haemophilus Influenzae Type B (Hib) Vaccines: Hib is one of the main bacterial causes of meningitis in children. Attachment of Hib polysaccharides to CRM197 produces an antigenic vaccine that has dramatically decreased the prevalence of Hib diseases in areas with administered immunity.
Advantages of CRM197 Over Other Carrier Proteins
- CRM197 has been shown to be highly immunogenic, this is in that once the immune system has been exposed to the carrier protein it is able to elicit a vigorous and persistent antibody response.
- This is especially because of the relatively younger population to which such vaccines are administered, and especially to infants and the young who are yet to develop immune systems.
- Since, CRM197 is non toxic, it can be incorporated in human vaccines without likely to cause symptoms similar to diphtheria. It also does not require chemical purification that oftentimes tasks the biochemical properties of the protein and weakens it.
- “The synthesis of CRM197 is not very complicated and can be easily carried out by adopting recombinant DNA technology, which has a long gestation period and low cost, thus the synthesis of CRM197 is relatively cheap compared to other reagents that are currently in use by the vaccine manufacturing industries.” Further, it can be synthesized in Escherichia coli or any other microbial system so that there is always a steady availability of the material.
- CRM197 has properties that can be exploited in various applications across many vaccines that target different pathogens. That there is a high immunogenicity of Aluminum to initiate immune response irrespective of the attached polysaccharide makes it appropriate as a carrier protein in conjugate vaccines for a wide range of conjugated.
How Does it Work?
The ability to produce CRM197 as a carrier protein depends on how the conjugated polysaccharide improves its immunogenicity. After the conjugated vaccine is delivered, the CRM197 moiety is taken up by antigen-presenting cells including dendritic cells. These cells then show portions of CRM197 to T-helper cells with major histocompatibility complex (MHC) class II molecules.
T-helper cell activation is, therefore, an essential event in the immune response process. On IgG activation, these cells act and help to produce antibodies specifically targeting the polysaccharide antigen. Not only does it stimulate the production of high affinity antibodies while increasing immunological memory, but the response itself is T-cell dependent.
Conclusion
Instead of targeting and changing the polysaccharide structure, the CRM197 carrier protein just made the immunogenicity and the effective response of the polysaccharide antigens much better. These are factors that have made it the backbone of the most effective vaccines especially in combating bacteria-caused diseases.
In this regard, based on the ongoing advancement of research in biotechnological aspects of the disease, CRM197 is expected to maintain a central focus in the progressive strategy in the development of vaccines to address both infectious diseases and other health issues including cancer. Its benefits to worldwide health, and breed prevention of childhood diseases, are a clear illustration of its importance in today’s medical practice.
