Protection by Natural Human Immunoglobulin M Antibody to Meningococcal Serogroup B Capsular Polysaccharide in the Infant Rat Protection Assay Is Independent of Complement-Mediated Bacterial Lysis

Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease develops with age, but the specificity and functional activity of natural antibodies associated with pro...

Full description

Saved in:
Bibliographic Details
Published in:Infection and Immunity 2005-08, Vol.73 (8), p.4694-4703
Main Authors: Toropainen, Maija, Saarinen, Leena, Wedege, Elisabeth, Bolstad, Karin, Michaelsen, Terje E, Aase, Audun, Käyhty, Helena
Format: Article
Language:English
Subjects:
Age Factors
Aluminum Hydroxide - metabolism
Animals
Bacterial Capsules - immunology
Bacteriology
Biological and medical sciences
Child
Complement System Proteins - immunology
Complement System Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Humans
Immunoblotting
Immunoglobulin G - analysis
Immunoglobulin G - immunology
Immunoglobulin M - immunology
Infant
Microbial Immunity and Vaccines
Microbiology
Miscellaneous
Neisseria meningitidis, Serogroup B - immunology
Phagocytosis - immunology
Polysaccharides, Bacterial - immunology
Rats
Serum - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease develops with age, but the specificity and functional activity of natural antibodies associated with protection are poorly understood. We addressed this question by using a selected subset of prevaccination sera (n = 26) with convergent or discrepant serum bactericidal activity (SBA) and infant rat protective activity (IRPA) against the serogroup B meningococcal strain 44/76-SL (B:15:P1.7,16) from Icelandic teenagers (B. A. Perkins et al., J. Infect. Dis. 177:683-691, 1998). The sera were analyzed by opsonophagocytic activity (OPA) assay, immunoblotting, immunoglobulin G (IgG) quantitation against live meningococcal cells by flow cytometry, and enzyme immunosorbent assay (EIA). High levels of SBA and OPA were reflected in distinct IgG binding to major outer membrane proteins and/or lipopolysaccharide in immunoblots. However, we could not detect any specific antibody patterns on blots that could explain IRPA. Only IgM antibody to group B capsular polysaccharide (B-PS), measured by EIA, correlated positively (r = 0.76, P < 0.001) with IRPA. Normal human sera (NHS; n = 20) from healthy Finnish children of different ages (7, 14, and 24 months and 10 years) supported this finding and showed an age-related increase in IRPA that coincided with the acquisition of B-PS specific IgM antibody. The protection was independent of complement-mediated bacterial lysis, as detected by the inability of NHS to augment SBA in the presence of human or infant rat complement and the equal protective activity of NHS in rat strains with fully functional or C6-deficient complement.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.73.8.4694-4703.2005