Vaccines to Overcome Antibiotic Resistance: The Challenge of Burkholderia cenocepacia

Scoffone, Viola Camilla; Barbieri, Giulia; Buroni, Silvia; Scarselli, María; Pizza, Mariagrazia; Rappuoli, Rino; Riccardi, Giovanna

doi:10.1016/j.tim.2019.12.005

Cited by 21 publications

(19 citation statements)

References 81 publications

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“…In this context, the development of protective vaccines against Bcc infections becomes highly attractive. To date, no such vaccine is available and only a few studies have been performed envisaging the identification of Bcc immunogenic proteins with the potential to originate a protective and lasting immune response [12][13][14]19,45,46].…”

Section: Discussionmentioning

confidence: 99%

“…PspA/IM30 family protein 13 In order to produce the proteins BCAL2645 and BCAL2022, the BCAL2645 and BCAL2022 genes were cloned into the expression vector pET23a+ under the control of the T7 promoter. Then, the overexpression of the proteins was achieved in E. coli as 6× His-tagged derivatives by induction with IPTG.…”

Section: Bcal2022mentioning

confidence: 99%

“…Since there is no eradication therapy presently available [11], new strategies to deal with Bcc infections are of major interest. Currently, no such strategies exist, but a wide variety of approaches and antigens are under study for the development of a possible vaccine against Bcc [12][13][14][15]. Bacteria use the proteins expressed on their surface to interact with their environment, being also exposed to the immune system of the host.…”

Section: Introductionmentioning

confidence: 99%

“…Since there is no eradication therapy presently available [ 11 ], new strategies to deal with Bcc infections are of major interest. Currently, no such strategies exist, but a wide variety of approaches and antigens are under study for the development of a possible vaccine against Bcc [ 12 , 13 , 14 , 15 ] .…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the Burkholderia cenocepacia J2315 Surface-Exposed Immunoproteome

et al. 2020

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Infections by the Burkholderia cepacia complex (Bcc) remain seriously life threatening to cystic fibrosis (CF) patients, and no effective eradication is available. A vaccine to protect patients against Bcc infections is a highly attractive therapeutic option, but none is available. A strategy combining the bioinformatics identification of putative surface-exposed proteins with an experimental approach encompassing the “shaving” of surface-exposed proteins with trypsin followed by peptide identification by liquid chromatography and mass spectrometry is here reported. The methodology allowed the bioinformatics identification of 263 potentially surface-exposed proteins, 16 of them also experimentally identified by the “shaving” approach. Of the proteins identified, 143 have a high probability of containing B-cell epitopes that are surface-exposed. The immunogenicity of three of these proteins was demonstrated using serum samples from Bcc-infected CF patients and Western blotting, validating the usefulness of this methodology in identifying potentially immunogenic surface-exposed proteins that might be used for the development of Bcc-protective vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Bcal2022mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Since there is no eradication therapy presently available [ 11 ], new strategies to deal with Bcc infections are of major interest. Currently, no such strategies exist, but a wide variety of approaches and antigens are under study for the development of a possible vaccine against Bcc [ 12 , 13 , 14 , 15 ] .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of the Burkholderia cenocepacia J2315 Surface-Exposed Immunoproteome

et al. 2020

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“…To overcome the limitations of genomics approaches like (1) mRNA expression levels does not represent the actual amount of active protein in a cell, (2) gene sequence gives incomplete information about post-translational modifications, and (3) genome information does not describe dynamic cellular processes; proteomics has been used in different ways to identify novel vaccine candidates against several human pathogens (Scoffone et al 2020;Sousa et al 2020;Sharma et al 2013;Rodriguez-Ortega et al 2006;Nilsson et al 2018;Zielke et al 2016;Couto et al 2016;Lo et al 2017). The present focus on using proteomics is to identify surface proteins in pathogens that can be targeted as potential vaccine candidates.…”

Section: Proteomics Approachesmentioning

confidence: 99%

Advanced strategies for development of vaccines against human bacterial pathogens

Sharma

Sanduja

Anand

et al. 2021

World J Microbiol Biotechnol

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Infectious diseases are one of the main grounds of death and disabilities in human beings globally. Lack of effective treatment and immunization for many deadly infectious diseases and emerging drug resistance in pathogens underlines the need to either develop new vaccines or sufficiently improve the effectiveness of currently available drugs and vaccines. In this review, we discuss the application of advanced tools like bioinformatics, genomics, proteomics and associated techniques for a rational vaccine design.

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Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

2022

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Brucella suis mediates the transmission of brucellosis in humans and animals and a significant facultative zoonotic pathogen found in livestock. It has the capacity to survive and multiply in a phagocytic environment and to acquire resistance under hostile conditions thus becoming a threat globally. Antibiotic resistance is posing a substantial public health threat, hence there is an unmet and urgent clinical need for immune-based non-antibiotic methods to treat brucellosis. Hence, we aimed to explore the whole proteome of Brucella suis to predict antigenic proteins as a vaccine target and designed a novel chimeric vaccine (multi-epitope vaccine) through subtractive genomics-based reverse vaccinology approaches. The applied subsequent hierarchical shortlisting resulted in the identification of Multidrug efflux Resistance-nodulation-division (RND) transporter outer membrane subunit (gene BepC) that may act as a potential vaccine target. T-cell and B-cell epitopes have been predicted from target proteins using a number of immunoinformatic methods. Six MHC I, ten MHC II, and four B-cell epitopes were used to create a 324-amino-acid MEV construct, which was coupled with appropriate linkers and adjuvant. To boost the immunological response to the vaccine, the vaccine was combined with the TLR4 agonist HBHA protein. The MEV structure predicted was found to be highly antigenic, non-toxic, non-allergenic, flexible, stable, and soluble. To confirm the interactions with the receptors, a molecular docking simulation of the MEV was done using the human TLR4 (toll-like receptor 4) and HLAs. The stability and binding of the MEV-docked complexes with TLR4 were assessed using molecular dynamics (MD) simulation. Finally, MEV was reverse translated, its cDNA structure was evaluated, and then, in silico cloning into an E. coli expression host was conducted to promote maximum vaccine protein production with appropriate post-translational modifications. These comprehensive computer calculations backed up the efficacy of the suggested MEV in protecting against B. suis infections. However, more experimental validations are needed to adequately assess the vaccine candidate's potential. Highlights• Subtractive genomic analysis and reverse vaccinology for the prioritization of novel vaccine target • Examination of chimeric vaccine in terms of allergenicity, antigenicity, MHC I, II binding efficacy, and structural-based studies • Molecular docking simulation method to rank based vaccine candidate and understand their binding modes

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Vaccines to Overcome Antibiotic Resistance: The Challenge of Burkholderia cenocepacia

Cited by 21 publications

References 81 publications

Characterization of the Burkholderia cenocepacia J2315 Surface-Exposed Immunoproteome

Characterization of the Burkholderia cenocepacia J2315 Surface-Exposed Immunoproteome

Advanced strategies for development of vaccines against human bacterial pathogens

Immunoinformatic-guided designing of multi-epitope vaccine construct against Brucella Suis 1300

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