| 摘要 |
A method is disclosed for producing a soluble conjugate vaccine, and preferably protein/polysaccharide conjugates. In this process, the polysaccharide is reacted with a reagent so as to provide a functional group on the polysaccharide molecule. Once the functional group is in place, the polysaccharide is reacted with a homobifunctional or heterobifunctional vinylsulfone to produce a vinylsulfone derivatized polysaccharide. Thereafter, the vinylsulfone derivatized polysaccharide is reacted with a protein to produce the conjugate. If desired, the protein may be derivatized with a functional group prior to the conjugation reaction step. In an alternative embodiment, the protein may be functionalized with a reactive group and then derivatized with the vinylsulfone group to produce a vinylsulfone derivatized protein. This protein may then be reacted with a polysaccharide to produce the conjugate. Optionally, the polysaccharide may be functionalized with a reactive group prior to the conjugation reaction. As another alternative, the polysaccharide may be derivatized directly with a pendant vinylsulfone of the crosslinking agent. The vinylsulfone derivatized polysaccharide may then be coupled to the protein (which may or may not be functionalized). In a similar manner, the protein may be derivatized directly with a pendant vinylsulfone of the crosslinking agent and then coupled to a polysaccharide molecule (which may or may not be functionalized).
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