Activity and cross-reactivity of antibodies induced in mice by immunization with a group B meningococcal conjugate.
The capsular polysaccharide of group B Neisseria meningitidis is composed of a linear homopolymer of alpha(2-8) N-acetyl neuraminic acid or polysialic acid (PSA) that is also carried by isoforms of the mammalian neural cell adhesion molecule (NCAM), which is especially expressed on brain cells during development. Here we analyzed the ability of antibodies induced by the candidate vaccine N-propionyl polysaccharide tetanus toxoid conjugate to recognize PSA-NCAM. We hyperimmunized mice to produce a pool of antisera and a series of immunoglobulin G monoclonal antibodies and evaluated their self-reactivity profile by using a battery of tests (immunoprecipitation, immunoblotting, and immunofluorescence detection on live cells and human tissue sections) chosen for their sensitivity and specificity to detect PSA-NCAM in various environments. We also searched for the effects of the vaccine-induced antibodies in two functional assays involving cell lysis or cell migration. Although they were highly bactericidal, all the antibodies tested showed very low or no recognition of PSA-NCAM, in contrast to PSA-specific monoclonal antibodies used as controls. Different patterns of cross-reactions were revealed by the tests used, likely due to affinity and specificity differences among the populations of induced antibodies. Furthermore, neither cell lysis nor perturbation of migration was observed in the presence of the tested antibodies. Importantly, we showed that whereas enzymatic removal of PSA groups from the surfaces of live cells perturbed their migration, blocking them with PSA-specific antibodies was not functionally detrimental. Taken together, our data indicated that this candidate vaccine induced antibodies that could not demonstrate an immunopathologic effect.
Coquillat
D
D
Laboratoire de Génétique et Physiologie du Développement, IBDM, CNRS/INSERM/Université de la Méditérranée/AP de Marseille, 13288 Marseille Cedex 9, France.
Bruge
J
J
Danve
B
B
Latour
M
M
Hurpin
C
C
Schulz
D
D
Durbec
P
P
Rougon
G
G
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules; D003429:Cross Reactions; D005260:Female; D006801:Humans; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D019006:Neural Cell Adhesion Molecules / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012794:Sialic Acids / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines; C051678:N-propyl group B meningococcal polysaccharide; D019006:Neural Cell Adhesion Molecules; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; D018074:Vaccines, Conjugate; C039455:capsular polysaccharide, meningococcal group B; C021319:polysialic acid