Rational Vaccine Design

Science Translational Medicine
13 July 2011 vol 3, issue 91

Research Articles
Vaccine Design
Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity
Maria Scarselli, Beatrice Aricò, Brunella Brunelli, Silvana Savino, Federica Di Marcello, Emmanuelle Palumbo, Daniele Veggi, Laura Ciucchi, Elena Cartocci, Matthew James Bottomley, Enrico Malito, Paola Lo Surdo, Maurizio Comanducci, Marzia Monica Giuliani, Francesca Cantini, Sara Dragonetti, Annalisa Colaprico, Francesco Doro, Patrizia Giannetti, Michele Pallaoro, Barbara Brogioni, Marta Tontini, Markus Hilleringmann, Vincenzo Nardi-Dei, Lucia Banci, Mariagrazia Pizza, and Rino Rappuoli
13 July 2011: 91ra62

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.

Vaccine Design
Science Translational Medicine Podcast: 13 July 2011
Rino Rappuoli and Orla Smith
13 July 2011: 91pc8