Anti-idiotypic antibody as a potential candidate vaccine for Neisseria meningitidis serogroup B.
Sepsis and meningitis caused by Neisseria meningitidis serogroup B (NMGB) are serious diseases in infants and young adults, but no effective vaccine is available. The capsular polysaccharide (PS) of NMGB has poor immunogenicity and a structural similarity to polysialic acid (PSA) on neuronal tissue that may elicit autoantibodies. Using HmenB3, a protective and nonautoreactive monoclonal antibody (MAb) to NMGB capsular PS, we produced an anti-idiotypic MAb, Naid60, which mimics the capsular PS of NMGB. We produced an anti-anti-idiotypic MAb, MoB34, by using the immunogenic site on Naid60 responsible for inducing the anti-NMGB PS antibody response. MoB34 elicited the complement-mediated killing of representative strains of serogroup B meningococci. MoB34 did not bind to CHP-134, a neuroblastoma cell line expressing alpha(2-8) PSA, or to mouse brain cryosections at a high concentration. Naid60-keyhole limpet hemocyanin immunization inhibited the growth of live NMGB in intraperitoneally challenged mice; in contrast, three of five control mice developed bacteremia. Thus, Naid60 has an immunogenic site that elicits antibodies with bactericidal activity against NMGB and no autoimmunity to PSA. We suggest that the immunogenic region of Naid60 is a candidate for the development of a new vaccine against NMGB.
Park
In Ho
IH
Department of Microbiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul.
Youn
Ju Ho
JH
Choi
In-Hong
IH
Nahm
Moon H
MH
Kim
Se Jong
SJ
Shin
Jeon-Soo
JS
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016667:Bacterial Capsules; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D020349:Surface Plasmon Resonance
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007135:Immunoglobulin Variable Region; D022401:Meningococcal Vaccines; C505460:Naid60 monoclonal antibody; D011135:Polysaccharides, Bacterial; C039455:capsular polysaccharide, meningococcal group B