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Investigation towards bivalent chemically defined glycoconjugate immunogens prepared from acid-detoxified lipopolysaccharide of Vibrio cholerae O1, serotype Inaba

Authors
  • Grandjean, Cyrille1, 2
  • Boutonnier, Alain1
  • Dassy, Bruno1
  • Fournier, Jean-Michel1
  • Mulard, Laurence A.1, 3
  • 1 Institut Pasteur, 25–28, Rue du Docteur Roux, Paris Cedex 15, 75724, France , Paris Cedex 15 (France)
  • 2 Université de Picardie Jules Verne, 33 Rue Saint Leu, Amiens, 80039, France , Amiens (France)
  • 3 Unité de Chimie des Biomolécules URA CNRS 2128, Institut Pasteur, 25–28, Rue du Docteur Roux, Paris Cedex 15, 75724, France , Paris Cedex 15 (France)
Type
Published Article
Journal
Glycoconjugate Journal
Publisher
Springer-Verlag
Publication Date
Jul 23, 2008
Volume
26
Issue
1
Identifiers
DOI: 10.1007/s10719-008-9160-6
Source
Springer Nature
Keywords
License
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Abstract

A free amino group present on the acid-detoxified lipopolysaccharide (pmLPS) of V. cholerae O1 serotype Inaba was investigated for site-specific conjugation. Chemoselective pmLPS biotinylation afforded the corresponding mono-functionalized derivative, which retained antigenicity. Thus, pmLPS was bound to carrier proteins using thioether conjugation chemistry. Induction of an anti-LPS antibody (Ab) response in BALB/c mice was observed for all conjugates. Interestingly, the sera had vibriocidal activity against both Ogawa and Inaba strains opening the way to a possible bivalent vaccine. However, the level of this Ab response was strongly affected by both the nature of the linker and of the carrier. Furthermore, no switch from IgM to IgG, i.e. from a T cell-independent to a T cell-dependent immune response was detected, a result tentatively explained by the possible presence of free polysaccharide in the formulation. Taken together, these results encourage further investigation towards the development of potent pmLPS-based neoglycoconjugate immunogens, fully aware of the challenge faced in the development of a cholera vaccine that will provide efficient serogroup coverage.

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