Optimization of the conjugation method for a serogroup B/C meningococcal vaccine

Biotechnol Appl Biochem. 2006 Nov;45(Pt 3):141-6. doi: 10.1042/BA20060041.

Abstract

A conjugate meningococcal vaccine against serogroup B/C consisting of capsular PS (polysaccharide) from serogroup C conjugated to OMV (outer membrane vesicle) from serogroup B would be a very useful vaccine in regions where there is a prevalence of both serogroups, for example in Brazil. For this purpose, the conjugation method that uses ADHy (adipic acid dihydrazide) as spacer and a carbodi-imide derivative, EDAC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide], as catalyser was optimized looking for synthesis yield and maintenance of the antigenicity of both components. The best synthesis conditions preserving the vaccine immunogenicity resulted in a final yield of approx. 17%. Immunogenicity of the vaccine was highest when 10% of the sialic acid residues of the PS were occupied by the ADHy spacer. Sterilization of the conjugate by filtration through a 0.22-microm-pore-size membrane resulted in a low recovery of protein and PS (approximately 50%), although the vaccine immunogenicity was maintained. Using gamma irradiation on freeze-dried sample, it was possible to maintain the integrity of OMV structure and, consequently, its ability to induce bactericidal antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipates / chemistry
  • Animals
  • Bacterial Capsules
  • Ethyldimethylaminopropyl Carbodiimide / chemistry
  • Female
  • Gamma Rays
  • Meningococcal Vaccines / immunology*
  • Meningococcal Vaccines / radiation effects
  • Mice
  • Polysaccharides, Bacterial / immunology*
  • Serum Bactericidal Test
  • Ultrafiltration
  • Vaccines, Conjugate / chemistry*
  • Vaccines, Conjugate / immunology*
  • Vaccines, Conjugate / radiation effects

Substances

  • Adipates
  • Meningococcal Vaccines
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate
  • capsular polysaccharide, meningococcal group B
  • meningococcal group C polysaccharide
  • Ethyldimethylaminopropyl Carbodiimide
  • adipic dihydrazide