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

Authors
  • Fukasawa, Lucila O
  • Schenkman, Rocilda P F
  • Perciani, Catia T
  • Carneiro, Sylvia M
  • Dias, Waldely O
  • Tanizaki, Martha M
Type
Published Article
Journal
Biotechnology and applied biochemistry
Publication Date
Nov 01, 2006
Volume
45
Issue
Pt 3
Pages
141–146
Identifiers
PMID: 16776648
Source
Medline
License
Unknown

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.

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