Understanding the Molecular Determinants Driving the Immunological Specificity of the Protective Pilus 2a Backbone Protein of Group B Streptococcus

Annalisa Nuccitelli, C. Daniela Rinaudo, Barbara Brogioni, Roberta Cozzi, Mario Ferrer-Navarro, Daniel Yero, John L. Telford, Guido Grandi, Xavier Daura, Martin Zacharias, Domenico Maione

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4 Citations (Scopus)

Abstract

The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molecular determinants driving the variant immunogenic specificity of BP-2a, in terms of single residue contributions, we generated six monoclonal antibodies against a specific protein variant based on their capability to recognize the polymerized pili structure on the bacterial surface. Three mAbs were also able to induce complement-dependent opsonophagocytosis killing of live GBS and target the same linear epitope present in the structurally defined and immunodominant domain D3 of the protein. Molecular docking between the modelled scFv antibody sequences and the BP-2a crystal structure revealed the potential role at the binding interface of some non-conserved antigen residues. Mutagenesis analysis confirmed the necessity of a perfect balance between charges, size and polarity at the binding interface to obtain specific binding of mAbs to the protein antigen for a neutralizing response. © 2013 Nuccitelli et al.
Original languageEnglish
Article numbere1003115
JournalPLoS Computational Biology
Volume9
DOIs
Publication statusPublished - 1 Jun 2013

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