Investigating the candidacy of LPS-based glycoconjugates to prevent invasive meningococcal disease : Immunology of glycoconjugates with high carbohydrate loading

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DOIResolve DOI: http://doi.org/10.1007/s10719-010-9309-y
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TypeArticle
Journal titleGlycoconjugate Journal
Volume27
Issue7-9
Pages643648; # of pages: 6
SubjectNeisseria meningitidis; Conjugate vaccine; LPS
AbstractWe investigated the immune responses of rabbits that were immunised with lipopolysaccharide (LPS)-based glycoconjugates by measuring the reactivity of the derived sera to a panel of selected wild-type and mutant strains of Neisseria meningitidis. In all cases, high titers of antibodies capable of recognising LPS elaborating the identical structure as presented on the immunising glycoconjugate were obtained, and in most cases the derived sera also recognised heterologous strains including wild-type, but at lower titers. However, although serum bactericidal antibodies were consistently obtained against strains elaborating the same LPS structure as the immunising antigen, this functional response was not observed against wild-type strains. We identified several potentially competing neoepitopes that had been introduced via our conjugation strategies, which might compete with the conserved inner core oligosaccharide target region, thus reducing the antibody titers to epitopes which could facilitate bactericidal killing. This study has therefore identified key factors that are crucial to control in order to increase the likelihood of obtaining bactericidal antibodies to wild-type meningococcal cells with LPS-derived glycoconjugates. Glycoconjugates utilised in this study, have been found to contain epitopes that do not contribute to the derivation of antibodies that may facilitate bactericidal killing of wildtype strains and must be avoided in future LPS-based glycoconjugate preparations.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number17401022
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Record identifier12f27170-cb5e-4254-8146-3c654347388d
Record created2011-03-25
Record modified2016-05-09
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