Novel vaccine candidates against Mycobacterium tuberculosis

Khoshnood, Saeed; Heidary, Mohsen; Haeili, Mehri; Drancourt, Michel; Darban-Sarokhalil, Davood; Nasiri, Mohammad Javad; Lohrasbi, Vahid

doi:10.1016/j.ijbiomac.2018.08.037

Cited by 33 publications

(25 citation statements)

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“…Membrane and exported proteins are crucial players for maintenance and survival of bacterial organisms in infected hosts, and their contribution to pathogenesis and immunological responses make these proteins relevant targets for biomedical research [7]. Consistently, various of the proteins identified in M. tuberculosis CFP were proposed as relevant mycobacterial virulence factors [44], putative active infection biomarkers [46] or vaccine candidates [70,71].…”

Section: Resultsmentioning

confidence: 89%

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

et al. 2020

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Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted and cell wall proteins interact with the host and play important roles in pathogenicity. These proteins are explored as candidate diagnostic markers, potential drug targets or vaccine antigens, and more recently special attention is being given to the role of their post-translational modifications. With the purpose of contributing to the proteomic and glycoproteomic characterization of this important pathogen, we performed a shotgun analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass spectrometry and a labelfree spectral counting normalization approach for protein quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the most abundant proteins belong to the extracellular region or cell wall compartment, and that the functional categories with higher protein abundance factor were virulence, detoxification and adaptation, and cell wall and cell processes. We could identify a group of proteins consistently detected in previous studies, most of which were highly abundant proteins. In culture filtrate, 140 proteins were predicted to contain one of the three types of bacterial N-terminal signal peptides. Besides, various proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the type VII secretion system using nonclassical secretion signals, were also identified. O-glycosylation was identified in 46 proteins, many of them lipoproteins and cell wall associated proteins. Finally, we provide proteomic evidence for 33 novel O-glycosylated proteins, aiding to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. These findings are expected to collaborate with the research on pathogen derived biomarkers, virulence factors and vaccine candidates, and to provide clues to the understanding of the pathogenesis and survival strategies adopted by M. tuberculosis.

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Section: Resultsmentioning

confidence: 89%

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

et al. 2020

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“…EsxA (Rv3875) and its chaperone protein EsxB (Rv3874), localized in Region of Difference 1 (RD1) of the MTB genome, are important virulence factors of MTB and the most immunodominant antigens thus far identified [59]. EsxA (or ESAT-6) is included in several vaccine candidates in development [60] and is also the core antigen in the IFN-γ release assays (IGRA) used to diagnose latent infection [61]. A former report described that an N-terminal Thr acetylation (+42Da) was identified in some species of this protein obtained in a short-term MTB culture filtrate [62] and other literature mentioned this protein as being glycosylated [17,63], however, to our knowledge, we are presenting novel evidence of several O-glycosylation events in this relevant secreted antigen.…”

Section: Resultsmentioning

confidence: 99%

“…Membrane and exported proteins are crucial players for maintenance and survival of bacterial organisms in infected hosts, and their contribution to pathogenesis and immunological responses make these proteins relevant targets for medical research [11]. Consistently, various of the proteins identified in M. tuberculosis CFP were proposed as relevant mycobacterial virulence factors [64], putative active infection biomarkers [9] or vaccine candidates [60,65]. This shotgun proteomic approach allowed a deep comprehension of M. tuberculosis H37Rv culture filtrate proteins reporting proteomic evidence in this sub-fraction for 1314 proteins.…”

Section: Resultsmentioning

confidence: 99%

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

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21 Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium 22 tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted 23 and cell wall proteins interact with the host and play important roles in pathogenicity. These 24 proteins have been explored as candidate diagnostic markers, potential drug targets or vaccine 25 antigens, and special attention has been given to the role of their post-translational 26 modifications. With the purpose of contributing to the proteomic characterization of this 27 important pathogen including an O-glycosylation profile analysis, we performed a shotgun 28 analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass 29 spectrometry and a label-free spectral counting normalization approach for protein 30 quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the 31 most abundant proteins belong to the extracellular region or cell wall compartment, and that 32 the functional categories with higher protein abundance factor were virulence, detoxification 33 and adaptation, and cell wall and cell processes. In culture filtrate, 140 proteins were predicted 34 to contain one of the three types of bacterial N-terminal signal peptides. Besides, various 35 proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the 36 type VII secretion system using nonclassical secretion signals, were also identified. O-37 glycosylation was identified as a frequent modification, being present in 108 proteins, principally 38 lipoproteins and secreted immunogenic antigens. We could identify a group of proteins 39 consistently detected in previous studies, most of which were highly abundant proteins. 40 Interestingly, we also provide proteomic evidence for 62 novel O-glycosylated proteins, aiding 41 to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. 48 HIV-positive people [1]. Although TB diagnosis and successful treatment averts millions of 49 deaths each year, there are still large and persistent gaps related to this infection that must be 50 resolved in order to accelerate progress towards the goal of ending the TB epidemic endorsed 51 by WHO [1]. 52 M. tuberculosis (MTB), has evolved successful mechanisms to circumvent the hostile 53 environment of the macrophage, such as inhibiting the phagosome-lysosome fusion and to 54 escape the acidic environment inside the phagolysosome [2]. MTB may be unique in its ability 55 to exploit adaptive immune responses, through inflammatory lung tissue damage, to promote 56 its transmission [3]. It has been proposed that this microorganism was pressed by an 57 evolutionary selection that resulted in an infection that induces partial immunity, where the 58 host survives a long period after being infected with the pathogen, aiding in microorganism 59 persistence and transmission [3]. MTB mechanisms of evasion of host immune system were 60 proposed to have c...

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“…The reader is also directed to Khoshnood et al . (2018) for a comprehensive review of novel vaccine candidates for TB currently at various stages of pre-clinical and clinical evaluation (108). …”

Section: Np Systems For Vaccination Against M Tuberculosismentioning

confidence: 99%

Mycobacterium Tuberculosis and Interactions with the Host Immune System: Opportunities for Nanoparticle Based Immunotherapeutics and Vaccines

et al. 2018

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Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a deadly infectious disease. The thin pipeline of new drugs for TB, the ineffectiveness in adults of the only vaccine available, i.e. the Bacillus Calmette-Guerin vaccine, and increasing global antimicrobial resistance, has rein vigorated interest in immunotherapies. Nanoparticles (NPs) potentiate the effect of immune modulating compounds (IMC), enabling cell targeting, improved transfection of antigens, enhanced compound stability and provide opportunities for synergistic action, via delivery of multiple IMCs. In this review we describe work performed in the application of NPs towards achieving immune modulation for TB treatment and vaccination. Firstly, we present a comprehensive review of M. tuberculosis and how the bacterium modulates the host immune system. We find that current work suggest great promise of NP based immunotherapeutics as novel treatments and vaccination systems. There is need to intensify research efforts in this field, and rationally design novel NP immunotherapeutics based on current knowledge of the mycobacteriology and immune escape mechanisms employed by M. tuberculosis.

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Novel vaccine candidates against Mycobacterium tuberculosis

Cited by 33 publications

References 74 publications

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Mycobacterium Tuberculosis and Interactions with the Host Immune System: Opportunities for Nanoparticle Based Immunotherapeutics and Vaccines

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