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Infection and Immunity, August 2005, p. 4694-4703, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4694-4703.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Maija Toropainen,1* Leena Saarinen,1 Elisabeth Wedege,2 Karin Bolstad,2 Terje E. Michaelsen,2 Audun Aase,2 and Helena Käyhty1

National Public Health Institute, Helsinki, Finland,1 Norwegian Institute of Public Health, Oslo, Norway2

Received 8 December 2004/ Returned for modification 14 January 2005/ Accepted 10 March 2005

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.

* Corresponding author. Mailing address: Vaccine Immunology Laboratory, Department of Vaccines, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland. Phone: 358-9-47448873. Fax: 358-9-47448599. E-mail: maija.toropainen{at}ktl.fi.

Editor: J. N. Weiser

Infection and Immunity, August 2005, p. 4694-4703, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4694-4703.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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