Development, characterization, and functional activity of a panel of specific monoclonal antibodies to inner core lipopolysaccharide epitopes in Neisseria meningitidis.
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.
Gidney
Margaret Anne J
MA
Institute for Biological Sciences, National Research Council, Ottawa, ON, K1A OR6, Canada. margaretanne.gidney@nrc-cnrc.gc.ca
Plested
Joyce S
JS
Lacelle
Suzanne
S
Coull
Philip A
PA
Wright
J Claire
JC
Makepeace
Katherine
K
Brisson
Jean-Robert
JR
Cox
Andrew D
AD
Moxon
E Richard
ER
Richards
James C
JC
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001770:Blood Bactericidal Activity; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008585:Meningitis, Meningococcal / Q000276:immunology; D008958:Models, Molecular; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D038542:Neisseria meningitidis, Serogroup C / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D009895:Opsonin Proteins; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D000939:Epitopes; D008070:Lipopolysaccharides; D009895:Opsonin Proteins