Carrier Protein Design

Polysaccharides from pathogenic bacteria can be made more immunogenic by chemical conjugation of them to carrier proteins. Such method produces a vaccine that effectively induces an immune response to the conjugated polysaccharide. This approach is a very important breakthrough for pediatric polysaccharide vaccines because, unlike adults, young children lack the ability to produce a protective immune response when the polysaccharide fraction itself is used. The discovery that polysaccharides conjugating to carrier proteins enhances immunogenicity and converted a T-cell independent to T-cell dependent antigens was one of the most important contemporary achievements in vaccinology, heralding a new era in vaccine development. In terms of the extensive experience in conjugate vaccine research, Creative Biolabs is proud to offer our customers professional design services and a series of carrier proteins with the best quality and most competitive price.

Types of Vaccine Carrier Proteins

To date, five carrier proteins have been used in licensed conjugate vaccines: tetanus toxoid (TT), diphtheria toxoid (DT), a genetically modified cross-reacting material (CRM) of diphtheria toxin, meningococcal outer membrane protein complex (OMPC) and H. influenzae protein D (HiD). Clinical trials have demonstrated the efficacy of these conjugate vaccines in preventing infectious diseases. All five of the carrier proteins are effective at increasing the immunogenicity of the vaccine but elicit different amounts of antibodies with different affinities. Additional carrier proteins that have been evaluated far less extensively in clinical trials include rEPA (Pseudomonas aeruginosa exotoxin A), KLH (keyhole limpet hemocyanin), and flagellin.

Carrier Proteins-Creative Biolabs

The vaccine carrier proteins we provide include:

  • Tetanus toxoid (TT): Tetanus toxin is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions.
  • Diphtheria toxoid (DT): Diphtheria toxin is an exotoxin secreted by Corynebacterium diphtheriae.
  • CRM197: CRM197 is a nontoxic variant of diphtheria toxin isolated from Corynebacterium diphtheriae C7 (β197) cultures. CRM197 differs from wild-type diphtheria toxin, in that a point mutation at amino acid position 52 substitutes glycine with glutamic acid, which eliminates enzymatic activity and toxicity. CRM197 is indistinguishable antigenically from diphtheria toxin but has advantages as a conjugate protein: it is nontoxic and has more lysyl side-chains available for conjugation.

  • Meningococcal outer membrane protein complex (OMPC): The Outer Membrane Protein Complex (OMPC) of the bacterium Neisseria meningitidis group B has been used successfully as a protein carrier in a Haemophilus influenza type b (Hib) polysaccharide conjugate vaccine and a Streptococcus pneumoniae (Pn) polysaccharide conjugate vaccine to elicit anti-polysaccharide immune responses in young infants.
  • H. influenzae protein D (HiD): Protein D (PD) is a highly conserved 42 kDa surface lipoprotein found in all Haemophilus influenzae, including nontypeable (NT) H. influenzae.
  • Keyhole limpet hemocyanin (KLH): Keyhole limpet hemocyanin is a large, multi-subunit, oxygen-carrying metalloprotein that is commonly used as a carrier protein and is widely used to assist haptens with lower immunogenicity to stimulate the immune system to produce antibodies. KLH is an effective carrier protein because of its large molecular weight, numerous epitopes, and rich lysine capable of coupling haptens. The cancer vaccine prepared by conjugating KLH to tumor-associated antigen can destroy tumor cells and exert anti-tumor immune response, so the research on the superior carrier protein KLH formulation in cancer vaccine is also increasing.

It has been shown that all carrier proteins enhance the immunogenicity of the polysaccharide upon conjugation with the protein carrier by various chemical manipulations. Creative Biolabs' vaccine carrier proteins are for research purposes only. However, GMP materials may be manufactured on a contract basis. If you plan to use toxoids of other native toxins as carriers or are interested in GMP manufacturing, please contact us.

Reference

  1. Pichichero, ME. (2013). “Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.” Hum Vaccin Immunother 9(12), 2505-2523.

Our services are for research use only. We do not provide services directly to individuals.

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