PT  - JOURNAL ARTICLE
AU  - Scarselli, Maria
AU  - Aricò, Beatrice
AU  - Brunelli, Brunella
AU  - Savino, Silvana
AU  - Di Marcello, Federica
AU  - Palumbo, Emmanuelle
AU  - Veggi, Daniele
AU  - Ciucchi, Laura
AU  - Cartocci, Elena
AU  - Bottomley, Matthew James
AU  - Malito, Enrico
AU  - Lo Surdo, Paola
AU  - Comanducci, Maurizio
AU  - Giuliani, Marzia Monica
AU  - Cantini, Francesca
AU  - Dragonetti, Sara
AU  - Colaprico, Annalisa
AU  - Doro, Francesco
AU  - Giannetti, Patrizia
AU  - Pallaoro, Michele
AU  - Brogioni, Barbara
AU  - Tontini, Marta
AU  - Hilleringmann, Markus
AU  - Nardi-Dei, Vincenzo
AU  - Banci, Lucia
AU  - Pizza, Mariagrazia
AU  - Rappuoli, Rino
TI  - Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity
AID  - 10.1126/scitranslmed.3002234
DP  - 2011 Jul 13
TA  - Science Translational Medicine
PG  - 91ra62--91ra62
VI  - 3
IP  - 91
4099  - http://stm.sciencemag.org/content/3/91/91ra62.short
4100  - http://stm.sciencemag.org/content/3/91/91ra62.full
AB  - 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.