CRM197 is a specialized protein that plays an important role in the development of modern vaccines. This protein helps the immune system of vaccinated individuals, particularly infants, develop strong and lasting protection against certain serious bacterial diseases. Its unique properties make it a valuable component in vaccine formulations. Understanding CRM197’s function helps clarify how some vaccines effectively protect against various pathogens.
What is CRM197 and How is it Made?
CRM197, or Cross-Reacting Material 197, is a modified version of diphtheria toxin, a substance produced by the bacterium Corynebacterium diphtheriae. While the original diphtheria toxin is dangerous, CRM197 has been genetically altered to be non-toxic. This modification involves a single amino acid substitution at position 52, where glutamic acid replaces glycine, which eliminates the toxin’s harmful ADP-ribosyltransferase activity.
This specific genetic change ensures that CRM197 cannot cause diphtheria disease symptoms, yet it retains structural similarities to the original toxin. Because it is genetically detoxified, CRM197 maintains its full complement of lysine amines, which are important for chemical conjugation. This allows it to be recognized by the immune system without posing any toxic threat. CRM197 is produced by cloning its gene into Corynebacterium diphtheriae, the same bacterium that produces the native toxin.
Its Crucial Role in Conjugate Vaccines
CRM197 is valued in vaccine development, especially for creating “conjugate vaccines.” These vaccines address a challenge in vaccinating young children against certain bacteria that are covered in polysaccharide (sugar-based) capsules. Infants and young children have immature immune systems that do not respond effectively to these polysaccharide antigens alone.
When polysaccharides are administered alone, they primarily activate B cells in a T-cell independent manner, leading to a weaker, shorter-lived immune response and limited immunological memory. CRM197 acts as a “carrier protein” by being chemically linked, or conjugated, to these bacterial polysaccharides. This linkage transforms the polysaccharide from a T-cell independent antigen to a T-cell dependent one.
The carrier protein allows the polysaccharide to be presented to T helper cells, which are important for a robust and long-lasting immune response. When the immune system encounters the conjugate, it recognizes the protein component, leading to T cell activation. These T cells then help B cells produce antibodies against the polysaccharide, resulting in stronger protection and the development of immunological memory, important for long-term immunity.
Key Vaccines That Use CRM197
CRM197 serves as a carrier protein in several widely used vaccines that have improved public health outcomes. An example is the pneumococcal conjugate vaccine, such as Prevnar 13 and Prevnar 20. These vaccines protect against infections caused by Streptococcus pneumoniae, which can lead to diseases like pneumonia, meningitis, and bloodstream infections.
CRM197 is also a component in some Haemophilus influenzae type b (Hib) conjugate vaccines. These vaccines target Haemophilus influenzae type b bacteria, which can cause severe invasive diseases, including meningitis and pneumonia, particularly in young children. Certain meningococcal conjugate vaccines, which protect against Neisseria meningitidis serogroups A, C, W, and Y, utilize CRM197 as a carrier protein.
Typhoid conjugate vaccines, designed to protect against typhoid fever caused by Salmonella Typhi, also use CRM197 as a protein carrier. The incorporation of CRM197 in these vaccines has enhanced their ability to elicit strong and durable immune responses, making them effective in preventing serious bacterial infections, especially in vulnerable populations like infants and young children.