TY - JOUR
T1 - Multi high-throughput approach for highly selective identification of vaccine candidates
T2 - The group a streptococcus case
AU - Bensi, Giuliano
AU - Mora, Marirosa
AU - Tuscano, Giovanna
AU - Biagini, Massimiliano
AU - Chiarot, Emiliano
AU - Bombaci, Mauro
AU - Capo, Sabrina
AU - Falugi, Fabiana
AU - Manetti, Andrea G.O.
AU - Donato, Paolo
AU - Swennen, Erwin
AU - Gallotta, Marilena
AU - Garibaldi, Manuela
AU - Pinto, Vittoria
AU - Chiappini, Nico
AU - Musser, James M.
AU - Janulczyk, Robert
AU - Mariani, Massimo
AU - Scarselli, Maria
AU - Telford, John L.
AU - Grifantini, Renata
AU - Norais, Nathalie
AU - Margarit, Immaculada
AU - Grandi, Guido
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2012/6
Y1 - 2012/6
N2 - We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flow-cytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.
AB - We propose an experimental strategy for highly accurate selection of candidates for bacterial vaccines without using in vitro and/or in vivo protection assays. Starting from the observation that efficacious vaccines are constituted by conserved, surface-associated and/or secreted components, the strategy contemplates the parallel application of three high throughput technologies, i.e. mass spectrometry-based proteomics, protein array, and flow-cytometry analysis, to identify this category of proteins, and is based on the assumption that the antigens identified by all three technologies are the protective ones. When we tested this strategy for Group A Streptococcus, we selected a total of 40 proteins, of which only six identified by all three approaches. When the 40 proteins were tested in a mouse model, only six were found to be protective and five of these belonged to the group of antigens in common to the three technologies. Finally, a combination of three protective antigens conferred broad protection against a panel of four different Group A Streptococcus strains. This approach may find general application as an accelerated and highly accurate path to bacterial vaccine discovery.
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U2 - 10.1074/mcp.M111.015693
DO - 10.1074/mcp.M111.015693
M3 - Article
C2 - 22286755
AN - SCOPUS:84862330001
SN - 1535-9476
VL - 11
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 6
ER -