Preparation method of bacterial polysaccharide and protein conjugate vaccine by using DSC as activating agent

Abstract

The invention discloses a preparation method of a bacterial polysaccharide and protein conjugate vaccine. The preparation method comprises the following step that before covalent binding of bacterial polysaccharide and protein, enabling bacterial polysaccharide and N,N'-disuccinimidyl carbonate (DSC) to generate activating reaction in an alkaline water solution with pH (potential of hydrogen) value of 8.0 to 9.5, so as to form the succinimidyl carbonate of the bacterial polysaccharide. The preparation method has the advantages that by using the N,N'-disuccinimidyl carbonate (DCS) as a bacterial polysaccharide activating agent, the toxicity is lower, the environment-friendly effect is realized, the cost is low, and the preparation cost of the vaccine is reduced; the activating time of polysaccharide is short, the number of steps is fewer, the whole binding cycle from polysaccharide activating to polysaccharide and protein binding is 4 to 5 days, the content of free polysaccharids is lower, and the animal immunogenicity is better.

Description

technical field [0001] The invention belongs to the technical field of vaccine preparation, and in particular relates to a preparation method of a bacterial polysaccharide-protein conjugated vaccine using DSC as an activator. Background technique [0002] At present, when preparing bacterial polysaccharide-protein conjugated vaccines at home and abroad, the bacterial polysaccharide activators used are cyanogen bromide (CNBr), 1-cyano-4-dimethylaminopyridine tetrafluoroborate (CDAP), sodium periodate , Carbodiimide (EDAC), these four kinds of polysaccharide activators have some deficiencies when activating bacterial polysaccharides. For example, CNBr is highly toxic. When it is used to activate bacterial polysaccharides, it will cause certain pollution to the environment and there are some safety hazards in use; although CDAP is not as toxic as CNBr, CDAP is relatively expensive, which increases the cost of vaccine manufacturing. ; Sodium periodate is used as a polysaccharid...

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Problems solved by technology

For example, CNBr is highly toxic, and when it is used for the activation of bacterial polysaccharides, it will cause certain pollution to the environment and there are some safety hazards in use; although CDAP is not as toxic as CNBr, the price of CDAP is relatively expensive, which increases the cost of vaccine manufacturing ;Sodium periodate is used as a polysaccharide activator, which destroys the polysaccharide structure, and oxidizes the hydroxyl group of the polysaccharide into an aldehyde group, and the whole reaction cycle is long, takes about 14 days, and the sodium periodate activation method has damage to the polysaccharide structure , there are many steps; EDAC, as a polysaccharide activator, has higher requirements on the polysaccharide structure, that is, the polysaccharide structure must contain free carboxyl groups, and EDAC activates the carboxyl groups in the polysaccharide and then connects with ADH to form polysaccharide-ADH derivatives

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