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Protective Immunization against Group B Meningococci Using Anti-Idiotypic Mimics of the Capsular Polysaccharide

Concetta Beninati^*, Simona Arseni, Giuseppe Mancuso^*, Walter Magliani, Stefania Conti, Angelina Midiri^*, Carmelo Biondo^*, Luciano Polonelli and Giuseppe Teti^1,*

^* Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, Messina, Italy; and Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia, Università degli Studi di Parma, Parma, Italy

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.

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