<i>In Silico</i>
            Identification of Epitopes in Mycobacterium avium subsp.
            <i>paratuberculosis</i>
            Proteins That Were Upregulated under Stress Conditions

Gurung, Ratna B.; Purdie, Auriol C.; Begg, Douglas J.; Whittington, Richard J.

doi:10.1128/cvi.00114-12

Cited by 29 publications

(24 citation statements)

References 42 publications

(46 reference statements)

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“…paratuberculosis compared to controls. In silico epitope prediction of MAP2698c and MAP3567 proteins found that they carry a higher number of T-cell epitopes than the other antigens examined (19). Transcriptomic studies have reported that genes encoding these four proteins are upregulated when exposed to different in vitro stress conditions (18,29,30).…”

Section: Discussionmentioning

confidence: 96%

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Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

Gurung

Begg

Purdie

et al. 2014

Clin Vaccine Immunol

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bJohne's disease in ruminants is a chronic infection of the intestines caused by Mycobacterium avium subsp. paratuberculosis. An important strategy to control disease is early detection, and a potentially efficient method for early detection is measurement of cell-mediated immune responses developed by the host in response to exposure or infection. One method is to measure lymphoproliferation and cytokine release from the host cells when exposed to the organism or parts of the organism. In this study, 10 recombinant M. avium subsp. paratuberculosis proteins known to be upregulated under in vitro stress conditions were evaluated by examining their ability to evoke memory as a result of exposure by vaccination or oral challenge with live Mycobacterium avium subsp. paratuberculosis. Out of 10 proteins, MAP2698c was found to induce higher cell-mediated immune responses in vaccinated and challenged sheep in comparison to healthy controls. The findings suggest that not all stress-regulated proteins have the diagnostic potential to detect cell-mediated immune responses in ovine paratuberculosis.

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Section: Discussionmentioning

confidence: 96%

“…paratuberculosis antigens were used to stimulate lymphoproliferation and IFN-␥ production (Table 1). Antigens were selected based on their upregulated transcriptomic (18) and proteomic (15,16) responses to physiological stress conditions and in silico epitope prediction analysis (19). Two M. avium subsp.…”

Section: Methodsmentioning

confidence: 99%

Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

Gurung

Begg

Purdie

et al. 2014

Clin Vaccine Immunol

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“…From this perspective, a new focus on the development of efficacious vaccines and sensitive diagnostic assays for the detection and eradication of MAP infection is necessary. Keeping all these in mind, a number of studies have been carried out in search of unique MAP-specific protein targets, which may elicit strong immune response in the host (Mustafa, 2005;Gumber et al, 2009;Gurung et al, 2012), but whole outer membrane proteome has not been analyzed yet to identify potential target antigens. The identification of MAP OMPs antigenic epitopes and understanding their interactions with the host MHC alleles and immune cells have enormous immunological value, which could be used for the development of vaccines and serodiagnostic assays against MAP.…”

Section: Discussionmentioning

confidence: 99%

“…It has a long incubation period, and available diagnostic tests are less sensitive, unsophisticated, time-consuming, and expensive (Rideout et al, 2003). The diagnosis of infection becomes effective as the disease advances to its clinical stage, but there is no single diagnostic test sensitive enough for the detection of early stages or subclinical infection (Gurung et al, 2012). It poses a serious challenge especially to ruminant production.…”

Section: Introductionmentioning

confidence: 99%

Proteome-wide B and T cell epitope repertoires in outer membrane proteins ofMycobacterium aviumsubsp.paratuberculosishave vaccine and diagnostic relevance: a holistic approach

2015

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Mycobacterium avium subsp. paratuberculosis (MAP) is an etiological agent of chronic inflammation of the intestine among ruminants and humans. Currently, there are no effective vaccines and sensitive diagnostic tests available for its control and detection. For this, it is of paramount importance to identify the MAP antigens, which may be immunologically recognized by the host immune system. To address this challenge, we performed identification of the immunogenic epitopes in the MAP outer membrane proteins (OMPs). We have previously identified 57 MAP proteins as OMPs [Rana A, Rub A, Akhter Y. 2014. Molecular BioSystems, 10:2329-2337] and have evaluated them for the epitope selection and analysis employing a computational approach. Thirty-five MAP OMPs are reported with nine-mer peptides showing high binding affinity to major histocompatibility complex (MHC) class I molecules and 28 MAP OMPs with 15-mer peptides of high binding affinity for MHC class II molecules. The presence of MHC binding epitopes indicates the potential cell-mediated immune response inducing capacity of these MAP OMPs in infected host. To further investigate the humoral response inducing properties of OMPs of MAP, we report potential B cell epitopes based on the sequences of peptide antigens and their molecular structures. We also report 10 proteins having epitopes for both B and T cells representing potential candidates which may invoke both humoral and cellular immune responses in the host. These findings will greatly accelerate and expedite the formulation of effective and cost-efficient vaccines and diagnostic tests against MAP infection.

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“…Because the cytokines interleukin 12 (IL-12), interferon γ (IFN- γ ), and IL-17 regulate the immune response during the course of infection, a study of specific cytokines may be an efficient way to define the immunological secreted proteins of M. bovis strains [ 16 ]. Immunoinformatic tools allow for the systemic identification of antigens, provide a basis for their experimental validation, and reduce the high cost of cloning and expressing genes encoding putative secreted proteins and the subsequent validation of individual proteins [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification of Novel Immunogenic Secreted Proteins of Mycoplasma bovis from Secretome Data and Experimental Verification

et al. 2020

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Mycoplasma bovis is a major pathogen, responsible for bovine respiratory diseases worldwide. The present lack of effective control measures leaves cattle owners at considerable perpetual risk of M. bovis outbreaks. In this study, we identified M. bovis secreted immunogenic proteins in silico as potential candidates for novel diagnostic agents and vaccines. We used immunoinformatics to analyze 438 M. bovis proteins previously identified with a label-free proteomics analysis of virulent M. bovis HB0801 (P1) and its attenuated P150 strains. The subcellular localization of these proteins was preliminarily screened and 59 proteins were found to be secreted extracellular proteins. Twenty-seven of these proteins contained a large number of predictive T-cell epitopes presented by major histocompatibility complex (MHC) class I and II molecules. Twenty-two of these 27 proteins had a high number of conformational B-cell epitopes, predicted from the corresponding 3D structural templates, including one unique to P1, two unique to P150, and 19 common to both strains. Five proteins were selected for further validation, and two of these, MbovP274 and MbovP570, were successfully expressed and purified. Both were confirmed to be secretory and highly immunogenic proteins that induced a mouse antibody response, reacted with cattle serum positive for M. bovis infection, and significantly increased the production of interleukin 8 (IL-8), IL-12 and interferon γ (IFN-γ) during the secretion of these three cytokines by both M. bovis mutants of these genes. These results should be useful in the development of novel immunological agents against M. bovis infection.

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In Silico Identification of Epitopes in Mycobacterium avium subsp. paratuberculosis Proteins That Were Upregulated under Stress Conditions

Cited by 29 publications

References 42 publications

Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

Lymphoproliferative and Gamma Interferon Responses to Stress-Regulated Mycobacterium avium subsp. paratuberculosis Recombinant Proteins

Proteome-wide B and T cell epitope repertoires in outer membrane proteins ofMycobacterium aviumsubsp.paratuberculosishave vaccine and diagnostic relevance: a holistic approach

In Silico Identification of Novel Immunogenic Secreted Proteins of Mycoplasma bovis from Secretome Data and Experimental Verification

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