Carbohydrate Conjugate Vaccine

Polysaccharides, on killed cells or purified, can produce protective immune responses. Vaccination with polysaccharides reduced the need to vaccinate with the organism itself. When the polysaccharides are coupled to a carrier protein, they produce a much higher titer. Creative Biolabs is a world leader in vaccine services. We provide personalized design and development strategies for carbohydrate conjugate vaccine.

Various pathogenic bacteria have polysaccharide coats, many with repeated epitopes. Although polysaccharide vaccines have been available for some time, they predominately produce IgM and are only moderately protective in adults, not in young children. Polysaccharide vaccines are less immunogenic in children under 2 years of age. Since the study found that the immunogenicity of polysaccharides can be enhanced by conjugating to proteins. At least four different bacterial-specific polysaccharide-protein conjugates have been used in production and clinical trials over the past two decades. These bacteria usually cause quite high mortality and morbidity, especially in young children.

Polysaccharide Vaccines

Polysaccharides are important virulence factors, especially for encapsulated bacteria which have a complex carbohydrate structure on their surface. Surface polysaccharides have several functions: they protect microorganisms from drying when exposed to the external environment; other capsular polysaccharides prevent the activation of alternative complement pathways, and sometimes they mimic the molecules produced by human cells so that our immune system does not remove pathogens recognized as foreign.

However, the polysaccharide vaccine does not completely solve the problem of bacterial diseases caused by encapsulated microorganisms. Bacterial polysaccharides are made from repeating units of monosaccharides linked together by glycosidic linkages. In addition, antibody responses to bacterial polysaccharides are weakly affected by adjuvants, IgM represent the major class of antibodies induced, and are not boosted by subsequent immunizations because their immune response does not induce memory. This is due to the fact that polysaccharides, unlike T cell-dependent (TD) antigens, are T-cell independent (TI) antigens. Polysaccharide antigens directly activate polysaccharide-specific B cells that differentiate into plasma cells to produce antibodies but do not form memory B cells.

Schematic diagram of mechanism of action for conjugate vaccines

Fig.1 Schematic diagram of mechanism of action for conjugate vaccines. (Costantino P, et al. 2011)

Glycoconjugate Vaccines

The limitations of polysaccharide vaccines have been overcome by covalent conjugation of carrier proteins as source of T cell epitopes. Since the concept was first applied to human vaccines, the first conjugate vaccine against Haemophilus influenzae type b (Hib) was subsequently developed. Many other glycoconjugate vaccines have been developed against bacterial pathogens such as Streptococcus pneumoniae, Neisseria meningitidis and group B Streptococcus. Today, glycoconjugate vaccine is one of the safest and most effective vaccines developed over the past 30 years.

Chemical conjugation of polysaccharides with protein carriers allows the processing of protein carriers by polysaccharide-specific B cells and presentation of the resulting peptides or glycopeptides associated with MHC class II on their surface. Further interaction with carrier-specific T cells then induces polysaccharide-specific B cell differentiation. Therefore, the conjugate vaccine has induced a T cell-dependent response early in life, leading to immune memory and promoting response through further doses of the vaccine.

Creative Biolabs is a world leader in vaccine services and provides our clients professional design services for carbohydrate conjugate vaccine development. Our scientists are confident in offering the best services and products upon request!

Reference

  1. Costantino P, Rappuoli R, Berti F. (2011). The design of semi-synthetic and synthetic glycoconjugate vaccines. Expert Opinion Drug Discovery. 6(10), 1045-1066.

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