We 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 neo-
epitopes 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 wild-type strains and must be avoided in future LPS-based
glycoconjugate preparations.