TT is a potent neurotoxin consisting of a light chain and a heavy chain responsible for cleaving synaptophysin. The heavy chain can be further divided into an N-terminal domain responsible for cell penetration and a C-terminal domain that controls TT neuron-specific binding.
Currently, TT is the primary carrier protein utilized in polysaccharide vaccines. It is derived from an exotoxin produced by Clostridium tetani bacteria. This exotoxin is detoxified using formaldehyde to eliminate its toxicity and then purified through chemical methods to obtain a highly pure toxoid by removing protein impurities. These refined toxoids have been employed as tetanus vaccines for a significant duration. Their remarkable immunogenicity and safety record make them the preferred choice as carrier molecules in the early phases of polysaccharide-protein conjugate vaccine development.
Fig.1 A vaccine candidate against Shigella flexneri 2a. (van der Put, et al., 2022)
CD BioGlyco provides conjugation of TT to Streptococcus pneumoniae polysaccharide antigen, Meningococcal polysaccharide antigen, and Haemophilus influenzae polysaccharide antigen through chemistry-based polysaccharide conjugation and physical crosslinking-based polysaccharide conjugation technology. Carbohydrates lack the ability to directly bind to MHC class II receptor molecules or be presented to T cells, rendering them truly T cell-independent. The absence of IgG memory induction by typical polysaccharide vaccines in mice has led to the belief that T cell assistance from glycoconjugates is a consequence of presenting MHC class II peptides to T cell receptors. Conjugate vaccines are composed of purified oligo- or polysaccharides, covalently linked to a carrier protein such as TT. These conjugate vaccines stimulate a T-cell-dependent antibody response, resulting in the production of high-affinity circulating antibodies and the establishment of immune memory in infants and other high-risk populations.
We provide capsular polysaccharide and TT conjugation services through the following procedures. First, the capsular polysaccharide is purified. The capsular polysaccharide is then mildly and selectively oxidized to formaldehyde groups using sodium metaperiodate. Verify the percentage of oxidized residues for trimethyl derivatives of coded samples using gas chromatography and/or mass spectrometry. To bind them to TT, combine each oxidized capsular polysaccharide with an equal amount of monomeric TT in sodium phosphate. Add sodium cyanoborohydride to each vial and incubate the mixture. The progress of the conjugation reaction, purification of the resulting conjugate, and protein and carbohydrate analysis of the purified vaccine are analyzed.
Fig.2 Coupling procedure for capsular polysaccharide and TT. (CD BioGlyco)
With several years of experience, CD BioGlyco is committed to making a difference in Carbohydrate-based Vaccine Development to meet your needs. Our world-class scientists and technicians will cooperate closely with our clients to accelerate the project. If you are interested in our services, please contact us for more details without any hesitation.
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