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Abstract
The sequence variability of protective antigens is a major challenge to the development of vaccines. For Neisseria meningitidis, the bacterial pathogen that causes meningitis, the amino acid sequence of the protective antigen factor H binding protein (fHBP) has more than 300 variations. These sequence differences can be classified into three distinct groups of antigenic variants that do not induce cross-protective immunity. Our goal was to generate a single antigen that would induce immunity against all known sequence variants of N. meningitidis. To achieve this, we rationally designed, expressed, and purified 54 different mutants of fHBP and tested them in mice for the induction of protective immunity. We identified and determined the crystal structure of a lead chimeric antigen that was able to induce high levels of cross-protective antibodies in mice against all variant strains tested. The new fHBP antigen had a conserved backbone that carried an engineered surface containing specificities for all three variant groups. We demonstrate that the structure-based design of multiple immunodominant antigenic surfaces on a single protein scaffold is possible and represents an effective way to create broadly protective vaccines.
Footnotes
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↵* These authors contributed equally to this work.
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Citation: M. Scarselli, B. Aricò, B. Brunelli, S. Savino, F. Di Marcello, E. Palumbo, D. Veggi, L. Ciucchi, E. Cartocci, M. J. Bottomley, E. Malito, P. Lo Surdo, M. Comanducci, M. M. Giuliani, F. Cantini, S. Dragonetti, A. Colaprico, F. Doro, P. Giannetti, M. Pallaoro, B. Brogioni, M. Tontini, M. Hilleringmann, V. Nardi-Dei, L. Banci, M. Pizza, R. Rappuoli, Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity. Sci. Transl. Med. 3, 91ra62 (2011).
- Copyright © 2011, American Association for the Advancement of Science
