Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

Phillips, Richard Odame; Phanzu, Delphin Mavinga; Beißner, Marcus; Badziklou, Kossi; Luzolo, Elysée Kalundieko; Sarfo, Fred Stephen; Halatoko, Wemboo Afiwa; Amoako, Yaw Ampem; Frimpong, Michael; Kabiru, Abass Mohammed; Piten, Ebekalisaï; Maman, Issaka; Bidjada, Bawimodom; Koba, Adjaho; Awoussi, Koffi Somenou; Kobara, Basile; Nitschke, Jörg; Wiedemann, Franz Xaver; Kere, Abiba Banla; Adjei, Ohene; Löscher, Thomas; Fleischer, Bernhard; Bretzel, Gisela; Herbinger, Karl‐Heinz

doi:10.1371/journal.pntd.0003457

Cited by 60 publications

(49 citation statements)

References 42 publications

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“…The high homology found with other pathogenic mycobacteria, such as M. leprae and M. ulcerans , might further extend their use as vaccine tools7778. Finally, the generic approach we have presented here can be applied for targeted discovery of antigens to be used in control measures for other infectious disease.…”

Section: Discussionmentioning

confidence: 82%

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Coppola

Meijgaarden

Franken

et al. 2016

Sci Rep

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New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.

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Section: Discussionmentioning

confidence: 82%

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Coppola

Meijgaarden

Franken

et al. 2016

Sci Rep

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“…A number of case-control studies allowed for the direct identification of potential risk factors for contracting the disease (Table 2). 6,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87] A review article evaluating identified risk factors was published in 2010. 88 …”

Section: Risk Factors and Transmissionmentioning

confidence: 99%

“…98,99 However, no evidence of a protective effect on the risk of developing BU was found in a number of case-control studies. 75,77,82,87 BCG vaccination may at least confer some protection against severe forms of BU.…”

Section: Bacillus Calmette-guérin Vaccinationmentioning

confidence: 99%

Epidemiology and disease burden of Buruli ulcer: a review

Röltgen¹,

Pluschke

2015

RRTM

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Buruli ulcer (BU) is a neglected tropical skin disease caused by Mycobacterium ulcerans. Infection foci occur mainly in remote, rural areas of Central and West Africa, but also in Australia and Papua New Guinea. In addition, infections caused by M. ulcerans strains of a different lineage are sporadically reported from scattered foci in Asia and the Americas. While in the past decade more than 42,000 BU cases have been reported worldwide, an assessment of the actual global disease burden is complicated by the remoteness of affected populations and a lack of data on the incidence of BU in a number of countries, from which cases have been historically reported. Moreover, as BU patients present with diverse clinical manifestations ranging from relatively unspecific nodules, plaques, or edema to necrotic, ulcerative lesions, differential diagnosis is manifold and thus clinical misclassification may occur. Since to date reservoirs and transmission pathways of M. ulcerans remain equivocal, early diagnosis and treatment of patients are key determinants to control the disease. Particularly in view of the apparent decline in BU incidence in regions of West Africa, awareness and knowledge of BU in endemic regions must be retained to ensure a continuous monitoring and control. An integrated approach for the control of tropical skin diseases should be considered to cope with this difficult task. This review article aims at providing an overview of the current global burden of BU and summarizes the state of knowledge on the various epidemiological aspects of this enigmatic disease.

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“…However, there is no consensus on the current distribution of this mycobacterial disease, except for 12 countries which constitute ⁓34,890 reported cases worldwide from 2007 to 2016 (Simpson et al 2019). Buruli ulcer has become the third most common mycobacterial disease after tuberculosis and leprosy (Phillips et al 2015;Huygen et al 2009). Although it may affect everyone irrespective of ages but the risk is the highest in the children (~15 years old) (Huygen et al 2009) and aged people (>50 years old) (N'krumah et al 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Buruli ulcer has become a major public health concern due to the lack of specific treatment and preventive measures (Simpson et al 2019;Johnson 2019;Singh et al 2019). Despite the effectiveness of antibiotics against Buruli ulcer, failures of treatment are common and the pathogen is prone to develop resistance (Phillips et al 2015). In addition, there is no effective vaccination available for preventing Buruli ulcer (Phillips et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans – An Integrated Vaccinomics Approach

Nain

Karim

Sen³

et al. 2019

Preprint

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Buruli ulcer is an emerging-necrotizing skin infection, responsible for permanent deformity if untreated, caused by the pathogen Mycobacterium ulcerans (M. ulcerans). Despite this debilitating condition, no specific disease-modifying therapeutics or vaccination is available. Therefore, we aimed to design an effective multi-epitope vaccine against M.ulcerans through an integrated vaccinomics approach. Briefly, the highest antigenic PE-PGRS protein was selected from which the promiscuous T-and B-cell epitopes were predicted. After rigorous assessment, 15 promising CTL, HTL and LBL epitopes were selected. The identified T-cell epitopes showed marked interactions towards the HLA binding alleles and provided 99.8% world population coverage. Consequently, a vaccine chimera was designed by connecting these epitopes with suitable linkers and adjuvant (LprG). The vaccine construct was antigenic and immunogenic as well as non-allergenic; hence, subjected to homology modelling. The molecular docking and dynamic simulation revealed strong and stable binding affinity between the vaccine and TLR2 receptor. The binding energy (∆G) and dissociation constant (Kd) were -15.3 kcal/mol and 5.9×10 -12 M, respectively. Further, disulfide engineering was applied to improve vaccine' stability and higher expression in Escherichia coli K12 system was ensured by codon optimization and cloning in silico.The computer-simulated immune responses were characterized by higher levels of IgM and IgG antibodies,helper T-cells with increased IFN-γ production, and macrophage activity crucial for immunity against M. ulcerans.Therefore, our data suggest that, if the designed vaccine is validated experimentally, it will prevent Buruli ulcer by generating robust immune response against M. ulcerans.

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Effectiveness of Routine BCG Vaccination on Buruli Ulcer Disease: A Case-Control Study in the Democratic Republic of Congo, Ghana and Togo

Cited by 60 publications

References 42 publications

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Epidemiology and disease burden of Buruli ulcer: a review

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans – An Integrated Vaccinomics Approach

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