SV-STAPH-VAX

Structural Vaccinology to drive the design and optimization of protein antigens for a multicomponent vaccine against Staphylococcus aureus

Coordinatore	GLAXOSMITHKLINE VACCINES SRL    more  Organization address address: Via Fiorentina 1 city: SIENA postcode: 53100 contact info Titolo: Dr. Nome: Francesco Cognome: Gulli Email: send email Telefono: +39 0577 243390 Fax: +39 0577 243085
Nazionalità Coordinatore	Italy [IT]
Totale costo	187˙414 €
EC contributo	187˙414 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2016-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	GLAXOSMITHKLINE VACCINES SRL  Organization address address: Via Fiorentina 1 city: SIENA postcode: 53100 contact info Titolo: Dr. Nome: Francesco Cognome: Gulli Email: send email Telefono: +39 0577 243390 Fax: +39 0577 243085	IT (SIENA)	coordinator	187˙414.80

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 Obiettivo del progetto (Objective)

'Staphylococcus aureus is one of the most important bacterial pathogens causing human death and disease on a global scale (Klevens, 2007). The rapid generation of antibiotic resistance, coupled with the frequency and severity of staphylococcal disease, underlie the increasing medical need to combat S. aureus infections. As an alternative to inadequate antibiotic therapies, we are dedicating efforts to develop a preventative staphylococcal vaccine. Previously, multiple capsular polysaccharides, or single antigenic proteins have been tested as staphylococcal vaccines, but all have failed in clinical trials, likely for reasons that we have reviewed (Bagnoli, 2012). Expert opinion now advocates a multi-protein vaccine strategy that could raise a broadly protective immune response, neutralizing pathogenic virulence factors like surface lipoproteins and families of secreted pore-forming toxins. To this end, we used Reverse Vaccinology to identify protective staphylococcal antigens that generated immunity in mice against diverse clinical S. aureus isolates (see Mishra, 2012). Additional candidates have been highlighted in the literature, including the leukotoxin LukED which targets the human CCR5 receptor (Alonzo, 2013). To ensure the development of efficacious and safe vaccine antigens, the research project proposes the structure-based optimization of two candidate antigens: (i) an antigen engineered from the Csa protein family that we recently discovered and characterized (Schluepen, 2013) and (ii) an engineered detoxified leukotoxin-E antigen. We recently determined and released the crystal structures of two Csa proteins and of LukE. As pioneers of Structural Vaccinology (Scarselli, 2011; Dormitzer, 2012), we are now ideally poised to exploit this high-resolution information which, coupled with our immunological data, represents an unprecedented knowledgebase to drive the development of a multicomponent vaccine to protect humans against staphylococcal disease.'