MODIFIED POLYSACCHARIDES FOR CONJUGATE VACCINES

摘要

The present invention relates to methods of manufacture of immunogenic glycoconjugates, in particular for use in pharmaceutical compositions for inducing a therapeutic immune response in a subject. The immunogenic glycoconjugates of the invention comprise one or more oligosaccharides or polysaccharides that are conjugated to one or more carrier proteins via an active aldehyde group. Accordingly, the invention provides methods of making (i) unsaturated microbial N-acyl derivative oligosaccharides or polysaccharides; (ii) novel conjugates of unsaturated N-acyl derivatives; and (iii) glycoconjugate compositions comprising conjugate molecules of fragments of microbial unsaturated N-acyl derivatives that serve as a covalent linker to one or more proteins. The invention further encompasses the use of the immunogenic glycoconjugates pharmaceutical compositions for the prevention or treatment of an infectious disease.

主权项

1. A method of making an immunogenic glycoconjugate comprising: a) substituting at least one N-acetyl group on an antigenic oligosaccharide or polysaccharide that comprises one or more N-acetyl substituted amino sugars by de-N-acetylating the at least one N-acetyl group to form an oligosaccharide or polysaccharide having at least one amino sugar comprising a primary amino group, then substituting the primary amino group with an N-acyl moiety comprising an unsaturated alkyl moiety of at least 5 carbons, wherein a double bond is located between two carbons other than between carbons 1 and 2 or between carbons 2 and 3 of the unsaturated alkyl moiety; b) contacting the oligosaccharide or polysaccharide with an oxidizing agent to generate at least one active aldehyde group at a site of unsaturation of said alkyl moiety; and c) conjugating the oligosaccharide or polysaccharide via the at least one active aldehyde group with a carrier protein; wherein the oligosaccharide or polysaccharide is an oligosaccharide or polysaccharide from Group B Streptococci, thereby generating an immunogenic glycoconjugate.