Multi high-throughput approach for highly selective identification of vaccine candidates: The group a streptococcus case

Giuliano Bensi, Marirosa Mora, Giovanna Tuscano, Massimiliano Biagini, Emiliano Chiarot, Mauro Bombaci, Sabrina Capo, Fabiana Falugi, Andrea G.O. Manetti, Paolo Donato, Erwin Swennen, Marilena Gallotta, Manuela Garibaldi, Vittoria Pinto, Nico Chiappini, James M. Musser, Robert Janulczyk, Massimo Mariani, Maria Scarselli, John L. TelfordRenata Grifantini, Nathalie Norais, Immaculada Margarit, Guido Grandi

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalMolecular and Cellular Proteomics
Volume11
Issue number6
DOIs
StatePublished - Jun 2012

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

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