Flagella hook protein FlgE is a novel vaccine candidate of Pseudomonas aeruginosa identified by a genomic approach

Wan, Chuang; Gao, Chen; Xie, Qiang; Wang, Yin; Cheng, Xin; Yao, Fang; Li, Yong; Zhang, Weijun; Zou, Quanming; Lu, Guangwen; Gu, Jiang

doi:10.1016/j.vaccine.2021.03.051

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…Among these candidates, alpha hemolysin (CctA), flagellin, and sialidase have been already considered as potential targets for subunit vaccines against the pathogen (Disasa et al 2020). Moreover, the immunogenicity of flagellar hook-basal body proteins including FlgE and FlgG were also revealed in both in silico and in vitro studies (Wilhelm et al 2006;Wan et al 2021). Besides these previously known candidates, three novel antigenic proteins, putative cell wall surface anchor family protein and two hypothetical proteins, were discovered in the current study.…”

Section: Discussionmentioning

confidence: 55%

Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach

Çolak

2021

Int J Pept Res Ther

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Blackleg is an infectious disease of animals that is commonly caused by Clostridium chauvoei and characterized by localized muscle necrosis. In this study, proteome-mining and immunoinformatics approaches were applied to identify novel antigenic proteins and to construct a multi-epitope vaccine against C. chauvoei. All proteins of C. chauvoei strains were retrieved from the NCBI Microbial Genome Database containing both genomic and proteomic data of prokaryotes. The proteins were analyzed to exclude non-redundant sequences and to determine antigenic, virulent, and non-allergenic vaccine candidates through several online tools, resulting in seven protein candidates. Cytotoxic T and B cell epitopes of these proteins were evaluated through the tools present in the immune epitope database and the prioritized antigenic epitopes were then conjugated via appropriate linkers to construct the vaccine candidate. After the evaluation of physicochemical properties of the construct, the tertiary structure was modeled and refined through trRosetta and GalaxyRefine, respectively. The quality of the 3D structure was validated by ERRAT score, z-score, and Ramachandran plot and the construct was then docked with bovine Toll-like receptor 4 (TLR 4) using ClusPro. The docked complex was subjected to Molecular Mechanics/Generalized Born Surface Area in the HawkDock server and normal mode analysis in the iMODS simulation suite to assess the binding energy and stability of the complex, respectively. Overall, the vaccine construct was found stable and energetically feasible for bovine TLR 4 binding. Therefore, it can be used as a multi-epitope vaccine construct in clostridial vaccines to control the blackleg disease.

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Section: Discussionmentioning

confidence: 55%

Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach

Çolak

2021

Int J Pept Res Ther

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“…Several studies had investigated the mechanism for the clearance of P. aeruginosa infections, but there is still no clear understanding on what immune response is required for an effective P. aeruginosa vaccine. Some studies highlighted the importance of humoral immune responses, 68 and others suggested a Th1-dominated immunity, 21,38,61,69 Th2-dominated immune responses, 38,70 or combination of humoral and cellular immunity 71 for the prevention of P. aeruginosa infection. Recent studies reported that Th17 responses 32,72−77 and some cell type mechanisms such as macrophages, 78 neutrophils, 79 and Th22 cells 80 might be required.…”

Section: ■ Discussionmentioning

confidence: 99%

“…aeruginosa vaccine. Some studies highlighted the importance of humoral immune responses, and others suggested a Th1-dominated immunity, ,,, Th2-dominated immune responses, , or combination of humoral and cellular immunity for the prevention of P. aeruginosa infection.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Antigen-Coated Polymer Particles Protects against Pseudomonas aeruginosa Infection

2022

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Pseudomonas aeruginosa is an opportunistic human pathogen that is intrinsically resistant to multiple antibiotics, causing severe and persistent infections in immunocompromised individuals. This bacterium has been listed as a priority pathogen by the WHO in 2017, and there is no vaccine available for human use. In this study, 10 vaccine candidate antigens were selected for particulate vaccine design. We engineered Escherichia coli to assemble biopolymer particles (BPs) that were either coated with epitopes (Ag) derived from OprF/I-AlgE proteins or PopB or PopB-Ag or coated with single or double copies of epitopes (10Ag and 10Ag(2x)) derived from OprF, OprI, AlgE, OprL, PopB, PilA, PilO, FliC, Hcp1, and CdrA. Antigen-coated BPs showed a diameter of 0.93−1.16 μm with negative surface charge. Antigens attached to BPs were identified by mass spectrometry. Vaccination with BP-Ag, BP-PopB, BP-PopBAg, PB-10Ag, and BP-10Ag(2x) with and without Alhydrogel adjuvant induced significant antigen-specific humoral and cell-mediated immune responses in mice. All particulate vaccines with Alhydrogel induced protection in an acute pneumonia murine model of P. aeruginosa infection, contributing to up to 80% survival when administered intramuscularly, and the addition of Alhydrogel boosted immunity. The BP-10Ag(2x) vaccine candidate showed the best performance and even induced protective immunity in the absence of Alhydrogel. Intramuscular administration of the BP-10Ag(2x) without Alhydrogel vaccine resulted in 60% survival. Intranasal vaccination induced immunity, contributing to about 90% survival. Overall, our data suggest that vaccination with BPs coated with P. aeruginosa antigens induce protective immunity against P. aeruginosa infections. The possibility of intranasal delivery will strongly facilitate administration and use of BP vaccines.

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“…These filamentous structures drive cell locomotion in fluids (swimming process) or on surfaces (swarming), allowing cells to move into favorable environments [ 49 ]. In this context, an in silico study on Pseudomonas aeruginosa , Morganella morganii and Clostridioides difficile introduced flagellar assembly proteins as valuable vaccine candidates [ 35 , 50 , 51 ]. Therefore, the identification of specific conserved domains in proteins provides essential information regarding their protective potential and possibly estimate their suitability for vaccine design.…”

Section: Discussionmentioning

confidence: 99%

Subtractive genomic analysis for computational identification of putative immunogenic targets against clinical Enterobacter cloacae complex

Bolourchi

Fereshteh²,

Goodarzi³

et al. 2022

PLoS ONE

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Background Enterobacter is a major nosocomial genus of Enterobacteriaceae responsible for a variety of nosocomial infections, particularly in prolonged hospitalized patients in the intensive care units. Since current antibiotics have failed treating colistin- and carbapenem-resistant Enterobacteriaceae, efforts are underway to find suitable alternative strategies. Therefore, this study conducted a reverse vaccinology (RV) to identify novel and putative immunogenic targets using core proteome of 20 different sequence types (STs) of clinical Enterobacter spp. Moreover, we introduced a structural-based approach for exploration of potential vaccine candidates against the Enterobacteriaceae family using their conserved domain analysis. Results A number of 2616 core coding sequences (CDSs) were retrieved from 20 clinical strains of Enterobacter spp. with a similarity of ≥ 50%. Nine proteins with a score of ≥ 20 considered as the shortlisted proteins based on the quartile scoring method, including three TonB-dependent receptors, WP_008500981.1, WP_058690971.1 and WP_058679571.1; one YjbH domain-containing protein, WP_110108068.1; three flagellar proteins, WP_088207510.1, WP_033145204.1 and WP_058679632.1; one spore-coat U domain-containing protein, WP_039266612.1; and one DD-metalloendopeptidase family protein, WP_025912449.1. In this study, proteins WP_058690971.1 and WP_110108068.1 were detected as the top candidates with regard to immune stimulation and interactions with TLRs. However, their efficacy is remaining to be evaluated experimentally. Conclusions Our investigation introduced common ferrichrome porins with high sequence similarity as potential vaccine candidates against the Enterobacteriaceae family. These proteins belong to the iron acquisition system and possess all criteria of suitable vaccine targets. Therefore, they need to be specifically paid attention for vaccine development against clinically important members of Enterobacteriaceae family.

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Flagella hook protein FlgE is a novel vaccine candidate of Pseudomonas aeruginosa identified by a genomic approach

Cited by 10 publications

References 31 publications

Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach

Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach

Intranasal Delivery of Antigen-Coated Polymer Particles Protects against Pseudomonas aeruginosa Infection

Subtractive genomic analysis for computational identification of putative immunogenic targets against clinical Enterobacter cloacae complex

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