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Reverse Vaccinology

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Front. Immunol. | doi: 10.3389/fimmu.2018.03021

Genome-based approach delivers vaccine candidates against Pseudomonas aeruginosa

 Irene Bianconi1, Beatriz Alcalá-Franco1,  Maria Sacrselli2,  Mattia Dalsass2, 3, Scilla Buccato2, Vega Masignani2 and  Alessandra Bragonzi1*
  • 1San Raffaele Scientific Institute (IRCCS), Italy
  • 2GlaxoSmithKline (Italy), Italy
  • 3Università degli Studi di Torino, Italy

High incidence, severity and increasing antibiotic resistance characterize Pseudomonas aeruginosa infections, highlighting the need for new therapeutic options. Vaccination strategies to prevent or limit P. aeruginosa infections represent a rational approach to positively impact the clinical outcome of risk patients; nevertheless this bacterium remains a challenging vaccine target. To identify novel vaccine candidates, we started from the genome sequence analysis of the P. aeruginosa reference strain PAO1 exploring the reverse vaccinology approach integrated with additional bioinformatic tools. The bioinformatic approaches resulted in the selection of 52 potential antigens. These vaccine candidates were conserved in P. aeruginosa genomes from different origin and among strains isolated longitudinally from cystic fibrosis patients. To assess the immune-protection of single or antigens combination against P. aeruginosa infection, a vaccination protocol was established in murine model of acute respiratory infection. Combinations of selected candidates, rather than single antigens, effectively controlled P. aeruginosa infection in the in vivo model of murine pneumonia. Five combinations were capable of significantly increase survival rate among challenged mice and all included PA5340, a hypothetical protein exclusively present in P. aeruginosa. PA5340 combined with PA3526-MotY gave the maximum protection. Both proteins were surface exposed by immunofluorescence and triggered a specific immune response. Combination of these two protein antigens could represent a potential vaccine to prevent P. aeruginosa infection.

Keywords: Pseudomonas aeruginosa, Reverse Vaccinolgy, Vaccine, respiratory infection, mouse model

Received: 17 Sep 2018; Accepted: 06 Dec 2018.

Edited by:

Pedro A. Reche, Complutense University of Madrid, Spain

Reviewed by:

Paola Massari, Tufts University School of Medicine, United States
Giampiero Pietrocola, Department of Molecular Medicine, University of Pavia, Italy  

Copyright: © 2018 Bianconi, Alcalá-Franco, Sacrselli, Dalsass, Buccato, Masignani and Bragonzi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Alessandra Bragonzi, San Raffaele Scientific Institute (IRCCS), Milan, Italy, bragonzi.alessandra@hsr.it