RT Journal Article
SR Electronic
T1 Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 91ra62
OP 91ra62
DO 10.1126/scitranslmed.3002234
VO 3
IS 91
A1 Scarselli, Maria
A1 Aricò, Beatrice
A1 Brunelli, Brunella
A1 Savino, Silvana
A1 Di Marcello, Federica
A1 Palumbo, Emmanuelle
A1 Veggi, Daniele
A1 Ciucchi, Laura
A1 Cartocci, Elena
A1 Bottomley, Matthew James
A1 Malito, Enrico
A1 Lo Surdo, Paola
A1 Comanducci, Maurizio
A1 Giuliani, Marzia Monica
A1 Cantini, Francesca
A1 Dragonetti, Sara
A1 Colaprico, Annalisa
A1 Doro, Francesco
A1 Giannetti, Patrizia
A1 Pallaoro, Michele
A1 Brogioni, Barbara
A1 Tontini, Marta
A1 Hilleringmann, Markus
A1 Nardi-Dei, Vincenzo
A1 Banci, Lucia
A1 Pizza, Mariagrazia
A1 Rappuoli, Rino
YR 2011
UL http://stm.sciencemag.org/content/3/91/91ra62.abstract
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.