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Peptide Mimics of the Group B Meningococcal Capsule Induce Bactericidal and Protective Antibodies after Immunization

Carla Lo Passo^*, Angela Romeo^*, Ida Pernice^*, Paolo Donato^*, Angelina Midiri, Giuseppe Mancuso, Milena Arigò, Carmelo Biondo, Roberta Galbo, Salvatore Papasergi, Franco Felici^*, Giuseppe Teti and Concetta Beninati^1,

^* Dipartimento di Scienze Microbiologiche, Genetiche e Molecolari, Dipartimento di Patologia e Microbiologia Sperimentale, and Dipartimento di Sanità Pubblica Veterinaria, Università degli Studi di Messina, Messina, Italy

Neisseria meningitidis serogroup B (MenB) is a leading cause of sepsis and meningitis in children. No vaccine is available for the prevention of these infections because the group B capsular polysaccharide (CP) (MenB CP) is unable to stimulate an immune response, due to its similarity with human polysialic acid. Because the MenB CP bears both human cross-reactive and non-cross-reactive determinants, we developed immunogenic peptide mimics of the latter epitopes. Peptides were selected from phage display libraries for their ability to bind to a protective anti-MenB CP mAb. One of these peptides (designated 9M) induced marked elevations in serum bactericidal activity, but not polysialic acid cross-reacting Abs, after gene priming followed by carrier-conjugate boosting. Moreover, the occurrence of bacteremia was prevented in infant rats by administration of immune sera before MenB challenge. 9M is a promising lead candidate for the development of an effective and affordable anti-MenB vaccine.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Address correspondence and reprint requests to Dr. Concetta Beninati, Dipartimento di Sanità Pubblica Veterinaria, Polo Universitario dell’Annunziata, Viale Annunziata, 98168 Messina, Italy. E-mail address: cbeninati{at}unime.it

² Abbreviations used in this paper: CP, capsular polysaccharide; MenB, Neisseria meningitidis serogroup B; PSA, polysialic acid; scFv, single chain variable fragment; KLH, keyhole limpet hemocyanin; pmIFN-, plasmid encoding for murine IFN-.

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