Whole genome identification of Mycobacterium tuberculosisvaccine candidates by comprehensive data mining and bioinformatic analyses

Zvi, Anat; Ariel, Naomi; Fulkerson, John P.; Sadoff, Jerald C.; Shafferman, Avigdor

doi:10.1186/1755-8794-1-18

Cited by 111 publications

(89 citation statements)

References 229 publications

(271 reference statements)

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“…Of the 23 immunogenic antigens we identified, 16 were in the list of these 189 antigens and 10 (Rv0079, Rv1733, Rv2028c, Rv2627c, Rv2629, Rv3132c, Rv1009, Rv0867c, Rv2389, and Rv1884c) were in the list of 45 top-hit antigens, while two (Rv0867 and Rv2627) were in the list of the 20 most immunodominant antigens identified by Zvi et al (53).…”

Section: Discussionmentioning

confidence: 77%

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Kassa

Ran

Geberemeskel

et al. 2012

Clin Vaccine Immunol

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e Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n ‫؍‬ 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-␥) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-␥ levels, >62 pg/ml) and 8 were strong inducers of IFN-␥ (IFN-␥ levels, >100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-␣), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-␥ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-␥, TNF-␣, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics.

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Section: Discussionmentioning

confidence: 77%

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Kassa

Ran

Geberemeskel

et al. 2012

Clin Vaccine Immunol

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“…Another significant finding is the detection of universal stress protein Rv2005c during reactivation. The Rv2005c is one of the DevR-regulated genes (71) and a predicted vaccine candidate (72). This protein is up-regulated during dormancy and reactivation.…”

Section: Validation Of Quantitative Proteomic Data By Qpcr-tomentioning

confidence: 99%

Profiling the Proteome of Mycobacterium tuberculosis during Dormancy and Reactivation

Gopinath

Raghunandanan

Gomez

et al. 2015

Molecular & Cellular Proteomics

113

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Tuberculosis, caused by Mycobacterium tuberculosis, still remains a major global health problem. The main obstacle in eradicating this disease is the ability of this pathogen to remain dormant in macrophages, and then reactivate later under immuno-compromised conditions. The physiology of hypoxic nonreplicating M. tuberculosis is well-studied using many in vitro dormancy models. However, the physiological changes that take place during the shift from dormancy to aerobic growth (reactivation) have rarely been subjected to a detailed investigation. In this study, we developed an in vitro reactivation system by re-aerating the virulent laboratory strain of M. tuberculosis that was made dormant employing Wayne's dormancy model, and compared the proteome profiles of dormant and reactivated bacteria using label-free onedimensional LC/MS/MS analysis. The proteome of dormant bacteria was analyzed at nonreplicating persistent stage 1 (NRP1) and stage 2 (NRP2), whereas that of reactivated bacteria was analyzed at 6 and 24 h post reaeration. Proteome of normoxially grown bacteria served as the reference. In total, 1871 proteins comprising 47% of the M. tuberculosis proteome were identified, and many of them were observed to be expressed differentially or uniquely during dormancy and reactivation. The number of proteins detected at different stages of dormancy (764 at NRP1, 691 at NRP2) and reactivation (768 at R6 and 983 at R24) was very low compared with that of the control (1663). The number of unique proteins identified during normoxia, NRP1, NRP2, R6, and R24 were 597, 66, 56, 73, and 94, respectively. We analyzed various biological functions during these conditions. Fluctuation in the relative quantities of proteins involved in energy metabolism during dormancy and reactivation was the most significant observation we made in this study. Proteins that are up-regulated or uniquely expressed during reactivation from dormancy offer to be attractive targets for therapeutic intervention to

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“…Many of the MPTR PPE proteins have a predicted beta-barrel outer membrane protein structure (reviewed in reference 26). An obvious but important question is whether there is a difference in PPE34 expression, location, antigenic potential, or function between PETRA strains with ETR A deletions compared to the PETRA strains that possess ETR A. Zvi et al (82) have reviewed antigenic and functional M. tuberculosis PPE proteins that could serve as vaccine candidates. It would be desirable to know whether putative PPE34 peptides are suitable candidates for vaccines.…”

Section: Effect Of the Etr A Locus On The Putative Ppe34 Proteinmentioning

confidence: 99%

“…Clusters of PE and PPE genes of Mycobacterium tuberculosis have been reported to be organized in operons (73). As already mentioned, PE (for example, PE-PGRS33 [70]) and PPE (for example, putative PPE34 [55]) proteins may be surface expressed and potentially contribute a large amount of the antigenic variation that affects immunity (17,82). A recent paper reporting genome-wide transcriptional profiling of chronic tuberculosis (69) did not focus on the PE/PPE protein families.…”

Section: Effect Of the Etr A Locus On The Putative Ppe34 Proteinmentioning

confidence: 99%

Polymorphic Exact Tandem Repeat A (PETRA): a Newly Defined Lineage ofMycobacterium tuberculosisin Israel Originating Predominantly in Sub-Saharan Africa

et al. 2009

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Whole genome identification of Mycobacterium tuberculosisvaccine candidates by comprehensive data mining and bioinformatic analyses

Cited by 111 publications

References 229 publications

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

Profiling the Proteome of Mycobacterium tuberculosis during Dormancy and Reactivation

Polymorphic Exact Tandem Repeat A (PETRA): a Newly Defined Lineage ofMycobacterium tuberculosisin Israel Originating Predominantly in Sub-Saharan Africa

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