Protective immunization against group B meningococci using anti-idiotypic mimics of the capsular polysaccharide.
Use of the serogroup B meningococcal capsular polysaccharide (MenB CP) as a vaccine is hampered by the presence of epitopes that cross-react with human polysialic acid. As non-cross-reactive, protective capsular epitopes have also been described, we set out to develop protein mimics of one of such epitopes using as a template a highly protective mAb (mAb Seam 3) raised against a chemically modified form of the MenB CP (N-Pr MenB CP). Using phage display, anti-idiotypic single-chain Ab fragments (scFvs) were obtained from spleen cells of mice immunized with the Seam 3 mAb. Two Seam 3-specific scFvs competed with N-Pr MenB CP for binding to either mAb Seam 3 or rabbit Abs present in typing sera. Moreover, in mice and rabbits the scFvs elicited the production of Abs reacting with both N-Pr MenB CP and whole meningococci, but not with human polysialic acid. These scFv-induced Ab responses were boostable and of the Th1 type, as shown by a predominance of IgG2a. In addition, passive immunization with sera from scFv-immunized animals partially protected neonatal mice from experimental infection with group B meningococci. In conclusion, we have produced anti-idiotypic scFvs that mimic a protective MenB CP epitope and may be useful in the development of an alternative group B meningococcal vaccine.
Beninati
Concetta
C
Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, Messina, Italy.
Arseni
Simona
S
Mancuso
Giuseppe
G
Magliani
Walter
W
Conti
Stefania
S
Midiri
Angelina
A
Biondo
Carmelo
C
Polonelli
Luciano
L
Teti
Giuseppe
G
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000096:biosynthesis / Q000378:metabolism; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D016667:Bacterial Capsules; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D001770:Blood Bactericidal Activity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007116:Immunization, Passive; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000378:metabolism; D008589:Meningococcal Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000145:classification* / Q000254:growth & development / Q000276:immunology*; D009895:Opsonin Proteins / Q000097:blood; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011817:Rabbits; D057127:Single-Chain Antibodies
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D007135:Immunoglobulin Variable Region; D022401:Meningococcal Vaccines; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D057127:Single-Chain Antibodies; C039455:capsular polysaccharide, meningococcal group B; C104215:scFv 421