Exploitation of Capsule Polymerases for Enzymatic Synthesis of Polysaccharide Antigens Used in Glycoconjugate Vaccines

Methods Mol Biol. 2021:2183:313-330. doi: 10.1007/978-1-0716-0795-4_16.

Abstract

The exploitation of recombinant enzymes for the synthesis of complex carbohydrates is getting increasing attention. Unfortunately, the analysis of the resulting products often requires advanced methods like nuclear magnetic resonance spectroscopy and mass spectrometry. Here, we use the capsule polymerases Cps4B and Cps11D from Actinobacillus pleuropneumoniae serotypes 4 and 11, respectively, as examples for the in vitro synthesis of capsule polymers similar to those used in glycoconjugate vaccine formulations. We demonstrate how substrate turnover in an enzymatic reaction can be analyzed by HPLC-based anion exchange chromatography and provide the protocol for separation and detection of UV-active polymer. Moreover, we describe how UV-inactive polymer can be separated and visualized using polyacrylamide gel electrophoresis followed by combined alcian blue-silver staining.

Keywords: Actinobacillus pleuropneumoniae; Alcian blue–silver staining; Capsular polysaccharide; Capsule polymerase; Enzymatic synthesis; Glycoconjugate vaccine; HPLC; In vitro vaccine production; PAGE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / isolation & purification
  • Bacterial Capsules / enzymology*
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Glycoconjugates / chemical synthesis*
  • Glycoconjugates / immunology
  • Glycoconjugates / isolation & purification
  • Polymers / chemical synthesis
  • Polysaccharides / chemical synthesis*
  • Polysaccharides / immunology
  • Polysaccharides / isolation & purification
  • Vaccines, Conjugate / chemistry*
  • Vaccines, Conjugate / immunology
  • Vaccines, Conjugate / isolation & purification

Substances

  • Antigens, Bacterial
  • Glycoconjugates
  • Polymers
  • Polysaccharides
  • Vaccines, Conjugate