Identification of a Universal Group B
            <i>Streptococcus</i>
            Vaccine by Multiple Genome Screen

Maione, Domenico; Margarit, Immaculada; Rinaudo, C. Daniela; Masignani, Vega; Mora, Marirosa; Scarselli, María; Tettelin, Hervé; Brettoni, Cecilia; Iacobini, Emilia Tiziana; Rosini, Roberto; D’Agostino, Nunzio; Miorin, Lisa; Buccato, Scilla; Mariani, Massimo A.; Galli, G.; Nogarotto, Renzo; Nardi‐Dei, Vincenzo; Vegni, Filipo; Fraser, Claire M.; Mancuso, Giuseppe; Teti, Giuseppe; Madoff, Lawrence C.; Paoletti, Lawrence C.; Rappuoli, Rino; Kasper, Dennis L.; Telford, John L.; Grandi, Guido

doi:10.1126/science.1109869

Cited by 512 publications

(415 citation statements)

References 21 publications

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“…It consists of in silico analysis of genomes from pathogens to select Drug Discovery Today Volume 14, Numbers 9/10 May 2009 REVIEWS ORFs encoding potentially antigenic exposed proteins, followed by large-scale screening of these antigens in immunization protocols using recombinant expression [34]. This high throughput approach has been successfully used to propose promising vaccine targets for prokaryote pathogens such as Neisseria meningitides [35] and Streptococcus agalactiae [36]. Reverse vaccinology has also been used for identifying potential vaccine candidates in the protozoa Trypanosoma cruzi and Leishmania [37][38][39].…”

Section: Introductionmentioning

confidence: 99%

Schistosomes—proteomics studies for potential novel vaccines and drug targets

DeMarco

Verjovski-Almeida

2009

Drug Discovery Today

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Schistosomiasis is a major health problem and, despite decades of research, only one effective drug, Praziquantel is currently available. Recent expansion of sequence databases on Schistosoma mansoni and S. japonicum has permitted a wealth of novel proteomic studies on several aspects of the organization and development of the parasite in the human host. This unprecedented accumulation of molecular data is allowing a more rational approach to propose drug targets and vaccine candidates, such as proteins located at the parasite surface. Successful preliminary trials of two vaccine candidates that have been detected at the parasite surface by proteomics give grounds for believing that such an approach may provide a fresh start for the field.

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Section: Introductionmentioning

confidence: 99%

Schistosomes—proteomics studies for potential novel vaccines and drug targets

DeMarco

Verjovski-Almeida

2009

Drug Discovery Today

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“…The increasing requirement for new vaccine-based preventive strategies, supplementing the antibiotic prophylaxis used for eradicating GBS colonization of the genital tract in pregnant women, has recently led to identification of antigens conferring broad protection in mice (23). The discovery of novel immunogenic virulence factors has also opened new perspectives to tackle GBS-associated infections (4,32).…”

Section: Discussionmentioning

confidence: 99%

Group BStreptococcusPullulanase Crystal Structures in the Context of a Novel Strategy for Vaccine Development

et al. 2009

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The group B streptococcus type I pullulanase (SAP) is a class 13 glycoside hydrolase that is anchored to the bacterial cell surface via a conserved C-terminal anchoring motif and involved in ␣-glucan degradation. Recent in vitro functional studies have shown that SAP is immunogenic in humans and that anti-SAP sera derived from immunized animals impair both group A and group B streptococcus pullulanase activities, suggesting that in vivo immunization with this antigen could prevent streptococcal colonization. To further investigate the putative role of SAP in bacterial pathogenesis, we carried out functional studies and found that recombinant SAP binds to human cervical epithelial cells. Furthermore, with a view of using SAP as a vaccine candidate, we present high-resolution crystal structure analyses of an N-terminally truncated form of SAP lacking the carbohydrate binding module but containing the catalytic domain and displaying glycosidase hydrolase activity, both in its apo form and in complex with maltotetraose, at resolutions of 2.1 and 2.4 Å, respectively.

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“…[73][74][75][76] The basic concept behind the reverse vaccinology approach is to use the complete genome sequence of a pathogen to identify a large number of novel protective antigens, express each candidate in recombinant form, and test each protein in one or more assays for capacity to confer immunological protection. Potential candidates are initially identified by computer analysis of the bacterial genome sequence with algorithms that predict secreted or surface-exposed proteins.…”

Section: Genome-wide Analysis and Therapeutics Research: Vaccinesmentioning

confidence: 99%

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

Musser

DeLeo

2005

The American Journal of Pathology

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Genome-wide analysis of microbial pathogens and molecular pathogenesis processes has become an area of considerable activity in the last 5 years. These studies have been made possible by several advances, including completion of the human genome sequence, publication of genome sequences for many human pathogens, development of microarray technology and high-throughput proteomics, and maturation of bioinformatics. Despite these advances, relatively little effort has been expended in the bacterial pathogenesis arena to develop and use integrated research platforms in a systems biology approach to enhance our understanding of disease processes. This review discusses progress made in exploiting an integrated genome-wide research platform to gain new knowledge about how the human bacterial pathogen group A Streptococcus causes disease. Results of these studies have provided many new avenues for basic pathogenesis research and translational research focused on development of an efficacious human vaccine and novel therapeutics. One goal in summarizing this line of study is to bring exciting new findings to the attention of the investigative pathology community. In addition, we hope the review will stimulate investigators to consider using analogous approaches for analysis of the molecular pathogenesis of other microbes.

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Identification of a Universal Group B Streptococcus Vaccine by Multiple Genome Screen

Cited by 512 publications

References 21 publications

Schistosomes—proteomics studies for potential novel vaccines and drug targets

Schistosomes—proteomics studies for potential novel vaccines and drug targets

Group BStreptococcusPullulanase Crystal Structures in the Context of a Novel Strategy for Vaccine Development

Toward a Genome-Wide Systems Biology Analysis of Host-Pathogen Interactions in Group A Streptococcus

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