Conjugation Method Design

The ability to reproducibly prepare hapten-carrier conjugates with consistent lot-to-lot protein yields and hapten densities is a key component in the development of hapten conjugate vaccines. This requires the development of suitable coupling chemistries to quantify hapten density without causing protein precipitation. Creative Biolabs is a world leader in vaccine services and provides conjugation method design for hapten conjugate vaccines.

Many naturally occurring proteins, peptides, carbohydrates, nucleic acids, and lipids as well as synthetic peptides are successful immunogens. Whereas, small chemical substances (haptens) are usually not good immunogens. However, they can become immunogenic when attached to carrier proteins. The immunogen must have epitopes that recognized by antigen presenting cells and T cell receptors and must be degradable. Hapten and the corresponding hapten-carrier conjugates are essential for the development of sensitive quantitative and qualitative immunoassays. Hapten, carrier proteins, coupling strategies, and hapten densities must be considered in designing hapten conjugates because the amount of hapten attached to the carrier affects the strength of the immune response against the newly generated antigenic determinant.

Structures of glycoconjugates

Fig.1 Structures of glycoconjugates.

There are currently two main approaches to prepare glycoconjugate vaccines based on different coupling chemistries:

  • One conjugation method is based on the random chemical activation of saccharide chains followed by covalent bonding with the protein carriers to obtain a cross-linked structure between the polysaccharide and the protein.
  • Another method is based on the generation by controlled fragmentation of the native polysaccharide, of appropriately sized oligosaccharides which are then activated at their terminal groups, usually with a linker molecule, and subsequently conjugated to the carrier protein obtaining a radial structure. Depending on the conjugation chemistry used, a chemical spacer can be used to facilitate conjugation of the protein to the carbohydrate antigen, and in some cases, conjugation chemistry also requires prior derivatization of the protein carrier.

Starting from suitable monosaccharides, the synthesis methods can provide pure and well-defined oligosaccharides for conjugation to protein carriers. A new method, called bioconjugation, is based on glyco-engineering the bacterial N-glycosylation pathway in bacteria such as E. coli. The polysaccharides that encoded by the inserted gene are produced on a polyisoprene carrier and then transferred to asparagine residues of a carrier protein that has to contain at least one (native or engineered) N-glycosylation site.

Our Services

Creative Biolabs is expert in the design and synthesis of conjugate vaccines, linking proteins to antigens such as haptens, oligosaccharides, polysaccharides, peptides, and proteins. We have diverse techniques used to couple haptens to carriers and provide guidance in the selection of the most appropriate procedure for a particular hapten.

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

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