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Philip A Coull

Publications and source records attributed to Philip A Coull.

4 recordsLinked to original sources
PubMed2003

Highly conserved Neisseria meningitidis inner-core lipopolysaccharide epitope confers protection against experimental meningococcal bacteremia.

Inner-core lipopolysaccharide (LPS) from Neisseria meningitidis is under investigation as a vaccine for prevention of meningococcal disease caused by N. meningitidis serogroup B (NmB). We investigated the functional activity of murine monoclonal antibody (MAb) B5 that recognizes a highly conserved (galE) LPS epitope. Three patterns of MAb reactivity were observed in N. meningitidis by Western blot, depending on the relative prevalence of sialylated, nonsialylated, and/or truncated LPS glycoforms. Three representative N. meningitidis strains (8047, M986, and 2996) were investigated with MAb B5 in functional assays in vitro and in vivo. MAb B5 completely protected infant rats against bacteremia caused by 8047, partially protected against 2996, and had no protective activity against M986. Thus, an inner-core LPS epitope can be a target for protective immunity, but the affinity of MAb B5 may only be sufficient to mediate protection against NmB strains possessing at least some truncated glycoforms.

Animals↗
PubMed2003

ELISA.

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Antigen-Antibody Complex↗
PubMed2002

Identification of a gene (lpt-3) required for the addition of phosphoethanolamine to the lipopolysaccharide inner core of Neisseria meningitidis and its role in mediating susceptibility to bactericidal killing and opsonophagocytosis.

We have identified a gene, lpt-3, that is required for the addition of phosphoethanolamine to the 3-position (PEtn-3) on the beta-chain heptose (HepII) of the inner core lipopolysaccharide (LPS) of Neisseria meningitidis (Nm). The presence of this PEtn-3 substituent is characteristic of the LPS of a majority ( approximately 70%) of hypervirulent Nm strains, irrespective of capsular serogroup, and is required for the binding of a previously described monoclonal antibody (mAb B5) to a surface-accessible epitope. All strains of Nm that have PEtn-3 possess the lpt-3 gene. In some lpt-3-containing strains, the 3-position on HepII is preferentially substituted by glucose instead of PEtn, the result of lgtG phase variation mediated by slippage of a homopolymeric tract of cytidines. Inactivation of lpt-3 resulted in loss of PEtn-3, lack of reactivity with mAb B5 and conferred relative resistance to bactericidal killing and opsonophagocytosis by mAb B5 in vitro. Thus, the identification of lpt-3 has facilitated rigorous genetic, structural and immunobiological definition of an immunodominant epitope that is a candidate immunogen for inclusion in an LPS-based vaccine to protect against invasive meningococcal disease.

Antibodies, Monoclonal↗