PA0833 Is an OmpA C-Like Protein That Confers Protection Against Pseudomonas aeruginosa Infection

Yang, Feng; Gu, Jiang; Zou, Jintao; Lei, Langhuan; Jing, Huaiqi; Zhang, Jin; Zeng, Hao; Zou, Quanming; Lv, Fenglin; Zhang, Jinyong

doi:10.3389/fmicb.2018.01062

Cited by 26 publications

(22 citation statements)

References 60 publications

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“…Some combination of these proteins, including OprF and OprI [48], or OprF and OprL [49], are currently investigated as vaccine candidates. Similarly, PA0833 was demonstrated is an OmpA C-like protein that induces a protective immune response in mice, indicating it as a promising antigen for vaccine development [50].…”

Section: Discussionmentioning

confidence: 99%

The Landscape of Pseudomonas aeruginosa Membrane-Associated Proteins

Motta

Vecchietti

Martorana

et al. 2020

Cells

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Background: Pseudomonas aeruginosa cell envelope-associated proteins play a relevant role in infection mechanisms. They can contribute to the antibiotic resistance of the bacterial cells and be involved in the interaction with host cells. Thus, studies contributing to elucidating these key molecular elements are of great importance to find alternative therapeutics. Methods: Proteins and peptides were extracted by different methods and analyzed by Multidimensional Protein Identification Technology (MudPIT) approach. Proteomic data were processed by Discoverer2.1 software and multivariate statistics, i.e., Linear Discriminant Analysis (LDA), while the Immune Epitope Database (IEDB) resources were used to predict antigenicity and immunogenicity of experimental identified peptides and proteins. Results: The combination of 29 MudPIT runs allowed the identification of 10,611 peptides and 2539 distinct proteins. Following application of extraction methods enriching specific protein domains, about 15% of total identified peptides were classified in trans inner-membrane, inner-membrane exposed, trans outer-membrane and outer-membrane exposed. In this scenario, nine outer membrane proteins (OprE, OprI, OprF, OprD, PagL, OprG, PA1053, PAL and PA0833) were predicted to be highly antigenic. Thus, they were further processed and epitopes target of T cells (MHC Class I and Class II) and B cells were predicted. Conclusion: The present study represents one of the widest characterizations of the P. aeruginosa membrane-associated proteome. The feasibility of our method may facilitates the investigation of other bacterial species whose envelope exposed protein domains are still unknown. Besides, the stepwise prioritization of proteome, by combining experimental proteomic data and reverse vaccinology, may be useful for reducing the number of proteins to be tested in vaccine development.

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Section: Discussionmentioning

confidence: 99%

The Landscape of Pseudomonas aeruginosa Membrane-Associated Proteins

Motta

Vecchietti

Martorana

et al. 2020

Cells

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“…While the first group could give the best protective immune response (6)(7)(8), it suffers from potential reactogenicity and risks when administrated to immunocompromised individuals (9). The second group including OMVs would produce a serotype-specific response with the outer membrane proteins being either difficult to purify or prepared as only the surface exposed portion of the antigen (4,(10)(11)(12). The third group (specific surface proteins) continues to include viable vaccine candidates since these surface exposed proteins are often responsible for pathogenesis and do not possess the reactogenicity or serotype specificity of the other candidates (4,5).…”

Section: Introductionmentioning

confidence: 99%

Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa

et al. 2020

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Infections caused by the opportunistic pathogen Pseudomonas aeruginosa can be difficult to treat due to innate and acquired antibiotic resistance and this is exacerbated by the emergence of multi-drug resistant strains. Unfortunately, no licensed vaccine yet exists to prevent Pseudomonas infections. Here we describe a novel subunit vaccine that targets the P. aeruginosa type III secretion system (T3SS). This vaccine is based on the novel antigen PaF (Pa Fusion), a fusion of the T3SS needle tip protein, PcrV, and the first of two translocator proteins, PopB. Additionally, PaF is made self-adjuvanting by the N-terminal fusion of the A1 subunit of the mucosal adjuvant double-mutant heat-labile enterotoxin (dmLT). Here we show that this triple fusion, designated L-PaF, can activate dendritic cells in vitro and elicits strong IgG and IgA titers in mice when administered intranasally. This self-adjuvanting vaccine expedites the clearance of P. aeruginosa from the lungs of challenged mice while stimulating host expression of IL-17A, which may be important for generating a protective immune response in humans. L-PaF’s protective capacity was recapitulated in a rat pneumonia model, further supporting the efficacy of this novel fusion vaccine.

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“…Therefore, while SG 9R is a rough strain with defective outer-core and O-antigen regions (O-Ag) of lipopolysaccharide (LPS), it may induce a different humoral immune response from field strains against OMP (8). The protective efficacy of OMP vaccines has already been established, and protective OMPs of S.enterica serovars have been identified for vaccine development (9,10).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Humoral Immune Responses to Different Forms of Salmonella enterica Serovar Gallinarum Biovar Gallinarum

Kim

et al. 2020

Front. Vet. Sci.

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Fowl typhoid is caused by Salmonella enterica serovar Gallinarum biovar Gallinarum (SG), and live attenuated, rough vaccine strains have been used. Both humoral and cellular immune responses are involved in protection, but the humoral responses to different forms of SG antigens are unclear. In this study, we compared humoral responses to a killed oil-emulsion (OE) smooth vaccine (SG002) and its rough mutant vaccine (SR2-N6) strains using proteomics techniques. We identified two immunogenic outer membrane proteins (OmpA and OmpX), and the selected linear epitopes were successfully applied in peptide-ELISA. Our peptide-and total OMP-ELISAs were used to compare the temporal humoral responses to various SG antigens: OE SG002 and SR2-N6; live, killed [PBS-suspension (PS) and OE)] and mixed (live and PS) formulations of another rough vaccine strain (SG 9R); and orally challenge with a field strain. Serum antibodies to the linear epitopes of OmpA and OmpX lasted only for the first 2 weeks, but serum antibodies against OMPs increased over time. The rough strain (SR2-N6) and mixed SG 9R induced higher serum antibody titers than the smooth strain (SG002) and single SG 9R (OE, live and PS SG 9R), respectively. Infection with the field strain delayed the serum antibody response by ∼2 weeks. Mucosal immunity was not induced by any formulation, except for infection with the field strain after SG 9R vaccination. Thus, our results may be useful to understand humoral immunity against various SG antigens and to improve vaccine programs and serological diagnosis in the field.

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PA0833 Is an OmpA C-Like Protein That Confers Protection Against Pseudomonas aeruginosa Infection

Cited by 26 publications

References 60 publications

The Landscape of Pseudomonas aeruginosa Membrane-Associated Proteins

The Landscape of Pseudomonas aeruginosa Membrane-Associated Proteins

Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa

Comparison of Humoral Immune Responses to Different Forms of Salmonella enterica Serovar Gallinarum Biovar Gallinarum

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