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Infection and Immunity, January 2004, p. 559-569, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.559-569.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Development, Characterization, and Functional Activity of a Panel of Specific Monoclonal Antibodies to Inner Core Lipopolysaccharide Epitopes in Neisseria meningitidis

Margaret Anne J. Gidney,^1,* Joyce S. Plested,^2,3, Suzanne Lacelle,¹ Philip A. Coull,^2,3 J. Claire Wright,² Katherine Makepeace,² Jean-Robert Brisson,¹ Andrew D. Cox,¹ E. Richard Moxon,² and James C. Richards¹

Institute for Biological Sciences, National Research Council, Ottawa, ON, K1A OR6, Canada,¹ Molecular Infectious Disease Group, University of Oxford Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DS,² Centre of Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom³

Received 19 June 2003/ Returned for modification 14 August 2003/ Accepted 24 September 2003

A panel of six murine monoclonal antibodies (MAbs) recognizing inner core lipopolysaccharide (LPS) epitopes of Neisseria meningitidis was prepared and characterized in order to determine the diversity of inner core LPS glycoforms among disease and carrier isolates. Two of these MAbs, L2-16 (immunoglobulin G2b [IgG2b]) and LPT3-1 (IgG2a), together with a third, previously described MAb, L3B5 (IgG3), showed reactivity, either individually or in combination, with all except 3 of 143 disease and carriage isolates (125 of 126 strains from blood, cerebrospinal fluid, or skin biopsy samples and 15 of 17 from nasopharyngeal cultures). MAbs L3B5, L2-16, and LPT3-1 were further characterized in an indirect immunofluorescence assay. All three MAbs bound to the bacterial cell surface, findings that correlated strongly with whole-cell enzyme-linked immunosorbent assay and immunodot blots. However, in contrast to our findings with L3B5, cell surface binding of L2-16 or LPT 3-1 did not correlate with functional activity as determined by bactericidal or infant rat passive protection assays against wild-type N. meningitidis strains. These findings are provocative with respect to the requirements for protective activity of antibodies and the development of inner core LPS vaccines against invasive meningococcal disease.

Editor: J. N. Weiser

M.A.J.G. and J.S.P. contributed equally to this work.

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