Chemically Modified Capsular Polysaccharides as Vaccines

Increasing the sialylation of therapeutic glycoproteins: The potential of the sialic acid biosynthetic pathway

“…Up to 150 sialic acid molecules can build polysialic acid 76. In bacteria, polysialic acid is often used as capsular polysaccharide, including neuroinvasive Escherichia coli K1 or Neisseria meningitidis group B 77. Polysialic acid is also uniquely expressed on the neural cell adhesion molecule of mammals 78.…”

Metabolic Glycoengineering with N‐Acyl Side Chain Modified Mannosamines

“…by chemical de-N-acetylation of the Neu5Ac residues or replacement of the N-acetyl groups by N-propionyl groups before conjugation to tetanus toxoid. [313][314][315] After administration to mice,t hese synthetic polySia glycoconjugates can induce bactericidal antibodies in high yields. [316][317][318] Furthermore,t he immunogenicity against N. menigitidis of serogroup Bc ould be augmented by introducing N-glycolyl, Npropyl, N-propionyl, or N-butanoyl analogues to trisaccharide fragments of the polysialylated O antigen.…”

Metabolic glycoengineering bacteria for therapeutic, recombinant protein, and metabolite production applications

“…An outstanding two-decade old example of this phenomenon are the polysialic acid capsules [97] that coat bacteria that live in a variety of harsh environments ranging from sewage to the human body, where the bugs are under assault from the host’s immune system. Insofar as one purpose of polysaccharide capsules is to shield pathogenic bacteria from the human immune system, the ability to chemically modify these sugars to render them immunogenic opens the door to new therapeutic strategies [98]. In the particular case of polysialic acid, it was also about 20 years ago that the Jennings’ group showed that a simple modification to the N -acyl group of sialic acid – specifically a one carbonyl extension of the N -acetyl group – provided the resulting “Sia5Prop” epitope with enhanced immunogenicity [99].…”