title: Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections.
abstract: Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.
authors: Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
authors: Annalisa
authors: A
authors: Nuccitelli
authors: Roberta
authors: R
authors: Cozzi
authors: Louise J
authors: LJ
authors: Gourlay
authors: Danilo
authors: D
authors: Donnarumma
authors: Francesca
authors: F
authors: Necchi
authors: Nathalie
authors: N
authors: Norais
authors: John L
authors: JL
authors: Telford
authors: Rino
authors: R
authors: Rappuoli
authors: Martino
authors: M
authors: Bolognesi
authors: Domenico
authors: D
authors: Maione
authors: Guido
authors: G
authors: Grandi
authors: C Daniela
authors: CD
authors: Rinaudo
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