Process for manufacturing vaccines

摘要

The present application discloses an improved method for conducting saccharide—protein conjugation reactions using carbodiimide condensation chemistry. Depending on the nature of the saccharide or protein carrier involved, the quality of the conjugate may be improved by adding one of the reaction components slowly to the reaction mixture. Immunogenic compositions are further provided comprising the saccharide-protein conjugates made by the methods disclosed.

主权项

1. A method of conjugating a saccharide to a protein carrier using carbodiimide condensation chemistry, wherein the saccharide has been derivatised to comprise either amino or carboxyl groups, and wherein the protein carrier comprises, or has been derivatised to comprise, both amino and carboxyl groups, said method comprising the steps of:
a) mixing the saccharide and aliquot of carbodiimide required to perform the conjugation, and b) adding the aliquot of protein carrier required over a period of 5 minutes to 6 hours; wherein the initial ratio of protein carrier to saccharide is 4:1 to 1:1 (w:w); and wherein the saccharide is a bacterial capsular saccharide derived from H. influenzae type b.