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  A mass spectrometry guided approach for the identification of novel vaccine candidates in gram-negative pathogens

Hornburg, D., Kruse, T., Anderl, F., Daschkin, C., Semper, R. P., Klar, K., et al. (2019). A mass spectrometry guided approach for the identification of novel vaccine candidates in gram-negative pathogens. SCIENTIFIC REPORTS, 9: 17401. doi:10.1038/s41598-019-53493-8.

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 Urheber:
Hornburg, Daniel1, Autor           
Kruse, Tobias2, Autor
Anderl, Florian2, Autor
Daschkin, Christina2, Autor
Semper, Raphaela P.2, Autor
Klar, Kathrin2, Autor
Guenther, Anna2, Autor
Mejias-Luque, Raquel2, Autor
Schneiderhan-Marra, Nicole2, Autor
Mann, Matthias1, Autor           
Meissner, Felix1, 3, Autor           
Gerhard, Markus2, Autor
Affiliations:
1Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              
2external, ou_persistent22              
3Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149678              

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Schlagwörter: HELICOBACTER-PYLORI INFECTION; AFFINITY PURIFICATION; SURFACE PROTEOME; GASTRIC-CANCER; SEROGROUP-B; BIOTINYLATION; PROTEINS; DATABASE; REVEALS; MARKER
 Zusammenfassung: Vaccination is the most effective method to prevent infectious diseases. However, approaches to identify novel vaccine candidates are commonly laborious and protracted. While surface proteins are suitable vaccine candidates and can elicit antibacterial antibody responses, systematic approaches to define surfomes from gram-negatives have rarely been successful. Here we developed a combined discovery-driven mass spectrometry and computational strategy to identify bacterial vaccine candidates and validate their immunogenicity using a highly prevalent gram-negative pathogen, Helicobacter pylori, as a model organism. We efficiently isolated surface antigens by enzymatic cleavage, with a design of experiment based strategy to experimentally dissect cell surface-exposed from cytosolic proteins. From a total of 1,153 quantified bacterial proteins, we thereby identified 72 surface exposed antigens and further prioritized candidates by computational homology inference within and across species. We next tested candidate-specific immune responses. All candidates were recognized in sera from infected patients, and readily induced antibody responses after vaccination of mice. The candidate jhp_0775 induced specific B and T cell responses and significantly reduced colonization levels in mouse therapeutic vaccination studies. In infected humans, we further show that jhp_0775 is immunogenic and activates IFN gamma secretion from peripheral CD4(+) and CD8(+) T cells. Our strategy provides a generic preclinical screening, selection and validation process for novel vaccine candidates against gram-negative bacteria, which could be employed to other gram-negative pathogens.

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Sprache(n): eng - English
 Datum: 2019
 Publikationsstatus: Online veröffentlicht
 Seiten: 16
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000498056900027
DOI: 10.1038/s41598-019-53493-8
 Art des Abschluß: -

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Titel: SCIENTIFIC REPORTS
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Seiten: - Band / Heft: 9 Artikelnummer: 17401 Start- / Endseite: - Identifikator: ISSN: 2045-2322