Polysaccharide-protein conjugate vaccines
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsChe-Hung Robert Lee, Carl E. Frasch
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Abstract
Methods for synthesis and manufacture of polysaccharide-protein conjugate vaccines at high yield are provided. The methods involve reaction of a hydrazide group on one reactant with an aldehyde or cyanate ester group on the other reactant. The reaction proceeds rapidly with a high conjugation efficiency, such that a simplified purification process can be employed to separate the conjugate product from the unconjugated protein and polysaccharide and other small molecule by-products.
Claims8
A method for preparing a conjugate vaccine, the method comprising:
- reacting a polysaccharide with 1-cyano-4-dimethylammoniumpyridinium tetrafluoroborate, whereby a solution of a cyanate-activated polysaccharide is obtained;
- reacting a protein with hydrazine or adipic acid dihydrazide in the presence of 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride at a pH of from 6 to 7, whereby a solution of a hydrazide-activated protein is obtained;
- raising the pH of the solution of the hydrazide-activated protein to from 7.0 to 11;
- buffer exchanging the solution of the hydrazide-activated protein to a pH of from 10.0 to 11.0;
- reacting the cyanate-activated polysaccharide with the hydrazide-activated protein at a pH of from 6 to 8 to yield a conjugate vaccine capable of stimulating an immune response.
Dependencies are inferred from the claim text.