Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats.
The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c-) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c- rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.
Toropainen
Maija
M
National Public Health Institute, Department of Vaccines, Vaccine Immunology Laboratory, Mannerheimintie 166, FIN-00300 Helsinki, Finland. maija.toropainen@ktl.fi
Saarinen
Leena
L
Vidarsson
Gestur
G
Käyhty
Helena
H
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D001770:Blood Bactericidal Activity; D003183:Complement C6 / Q000502:physiology*; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D051379:Mice; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D018272:Porins / Q000276:immunology*; D051381:Rats
D000907:Antibodies, Bacterial; D003183:Complement C6; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D018272:Porins; C057699:porin protein, Neisseria