CRM197 polysaccharide vaccine and conjugate vaccine carrier protein

Recombinant CRM197 (diphtheria toxin non-toxic mutant protein)-CRM197 polysaccharide vaccine and conjugate vaccine carrier protein

• It is a recombinant protein based on BG Recombinant Expression Platform expressed in Escherichia coli prokaryotic system with clear research results

• Based on GMP production and quality management standards, we provide compliance with the core requirements of GMP quality system and stable performance

• HPLC purity is above 95%, and the efficiency is much higher than other competitors under the same dosage conditions

• Has good immunogenicity: T cell and B cell epitopes are better preserved

• Can bind with various molecules and membranes, unaffected by temperature and pH: suitable for various experimental conditions, with good tolerance

• No animal source, no need for formaldehyde detoxification, more stable: no formaldehyde detoxification residue, used as a vaccine, especially for immunization of infants and young children, with higher biological safety

• The lysine groups on the surface of CRM197 can be fully utilized for binding reactions, improving binding efficiency: polysaccharide linkage can be mediated by linker molecules (such as succinic acid)

CRM197 is a non-toxic mutant protein of diphtheria toxin（CRM197 polysaccharide vaccine and conjugate vaccine carrier protein）

It is a non-toxic diphtheria toxin mutant that replaces C2H5NO2 at position 52 with C5H9NO4 as a single mutation, causing changes in the active site of diphtheria toxin enzyme and thus unable to produce toxic effects on cells. However, it still maintains the same antigenicity and immunogenicity as natural diphtheria toxin, making it a safe carrier in combination vaccines.

It has gradually been widely applied in commercial settings, such as preventive vaccines against meningococcal, Haemophilus influenzae type B, and pneumococcal infections, and has also been widely used in the prevention and treatment of various diseases that harm human health, such as cancer, viruses, allergies, and Alzheimer's disease.

CRM197 protein structure diagram:

CRM197 protein GLU52 mutation site

Basic characteristics:

Single amino acid substitution in fragments

Conformational changes occur when binding to a single cloned antibody

Binding with phospholipid bilayer

Having the same chain length as diphtheria toxin

Can indirectly connect other molecules

Testing non-toxic in animal models

It is possible to mass produce many vaccines for commercial disciplines in a culture medium with clear ingredients

A better 'ferry' than diphtheria toxoid

CRM197 itself also has a certain degree of immunogenicity, producing lower levels of anti diphtheria toxin antibodies than diphtheria toxoid, and will not "overshadow" others, demonstrating its advantages as a binding vaccine carrier: it presents polysaccharide antigens better than diphtheria toxoid and is willing to "cross the boat"

Application fields

• Application of bacterial infectious disease vaccines: development of vaccines for various bacterial infectious diseases such as HIB vaccine, pneumonia vaccine, meningococcal vaccine, tuberculosis, typhoid fever, group A streptococcus, and melioidosis. Additionally, CRM197 can be developed as an intranasal vaccine, such as for Group C meningococcal bacteria

• Participate in cancer treatment: CRM197 is non-toxic but can inhibit the growth and proliferation of cancer cells. Research has shown that CRM197 inhibits tumor formation by binding to soluble forms of epidermal growth factor HB-EGF and its precursors, preventing its activation of ErbB receptors to interrupt protein synthesis, hinder mitosis, and thus inhibit tumor formation. CRM197 can synergistically inhibit the development of ovarian cancer with C47H51NO14; It can also be used as a chemical sensitizer to enhance the cytotoxicity of gemcitabine (an anti-tumor drug) in human glioma cells; It can also help drugs pass through the blood-brain barrier and treat brain tumors. In addition, CRM197 is more involved in cancer immunotherapy as a cancer vaccine carrier, and plays an important role in the treatment and prevention of many cancers, such as glioma, pancreatic cancer, oral cancer, leukemia, triple negative breast cancer, and adrenal cortical cancer.

• Participate in the research and development of viral vaccines:

• Influenza vaccine: CRM197, as a stable and effective carrier protein, is also used in the development of a new type of influenza A virus vaccine. Compared to using the constant epitope (M2e) of the H1N1 virus alone as an antigen, the M2e-CRM197 antigen bound to CRM197 has higher immunogenicity.

• Hepatitis E vaccine: The new hepatitis E vaccine designed based on CRM197 has shown better performance compared to the existing p239 vaccine. The catalytic domain of CRM197 binds to epitope protein E2 to form CRM197 (A) - E2 antigen, which exhibits higher immunogenicity in mice. A dose of 1 μ g of CRM197 (A) - E2 can protect vaccinated monkeys from hepatitis E virus attacks, while the p239 vaccine requires a higher dose (10 μ g).

• Zika virus vaccine: The structural domain III (EDIII) of the Zika virus (ZIKV) E protein coupled with CRM197 induced high EDIII specific antibody titers in mice, solving the problem of low immunogenicity of EDIII and potentially becoming a candidate vaccine for preventing Zika.

• Participate in the prevention and treatment of various diseases:

• Prevention and treatment of fungal diseases: The seaweed polysaccharide CRM197 conjugate vaccine has been proven to protect mice from fungal infections and is expected to participate in the prevention and treatment of fungal diseases including Candida albicans and Aspergillus fumigatus.

• Smoking cessation vaccine: The application of CRM197 in the development of anti nicotine vaccines and other vaccines will help improve smoking cessation and drug rehabilitation rates.

• Treating allergic diseases: CRM197 as a carrier protein has the potential to treat allergic diseases. In a study on allergen specific immunotherapy for dust mites (HDM), researchers coupled allergen Derp2 with CRM197 as a vaccine and injected it into mice. They found that it could induce rDerp2 specific IgG1 antibodies, reduce IgE reactivity, and inhibit asthma airway inflammation.