Understanding the molecular determinants driving the immunological specificity of the protective pilus 2a backbone protein of Group B Streptococcus
Nuccitelli, Annalisa (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Rinaudo, C. Daniela (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Brogioni, Barbara (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Cozzi, Roberta (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Ferrer-Navarro, Mario (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Yero, Daniel (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Telford, John L. (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Grandi, Guido (Novartis Vaccines and Diagnostics (Siena, Itàlia))
Daura i Ribera, Xavier (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Zacharias, Martin (Technical University Munich. Physics Department)
Maione, Domenico (Novartis Vaccines and Diagnostics (Siena, Itàlia))

Fecha:	2013
Resumen:	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.
Ayudas:	European Commission 037325
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; Versió publicada
Materia:	Antigens ; Pili and fimbriae ; Bacterial pathogens ; Complement system ; Monoclonal antibodies ; Immune system proteins ; Sequence alignment
Publicado en:	PLOS Computational Biology, Vol. 9, Issue 6 (June 2013) , p. e1003115, ISSN 1553-734X

DOI: 10.1371/journal.pcbi.1003115
PMID: 23825940

11 p, 7.8 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Instituto de Biotecnología y de Biomedicina (IBB)
Artículos > Artículos publicados