Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.102
Filtrar
1.
Iran J Allergy Asthma Immunol ; 20(1): 106-113, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33639625

RESUMO

Bacillus Calmette Guerin (BCG) was designed for protecting children against tuberculosis. Also, it can protect against other infectious diseases through the induction of trained immunity. Due to its heterologous protective effects, the BCG vaccine has been proposed as atreatment option for coronavirus disease-2019 (COVID-19). Epidemiological studies have found that countries without BCG vaccination policy have experienced higher mortality rates related toCOVID-19 infection than those with BCG vaccination policy. However, there are some confounding factors such as age, population intensity, immigration, the pandemic phase, and data accuracy that may affect these results. Therefore, this hypothesis should be evaluated by clinical trial studies. Large-scale clinical trials are in progress to investigate ifthe BCG vaccine could be used as a useful tool for protection against COVID-19 infection.


Assuntos
Vacina BCG/imunologia , Mycobacterium bovis/imunologia , Tuberculose/epidemiologia , /imunologia , Criança , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Pandemias , Políticas , Tuberculose/imunologia , Vacinação
2.
Vaccine ; 38(48): 7629-7637, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33071000

RESUMO

This work demonstrates the presence of immune regulatory cells in the cervical lymph nodes draining Bacillus Calmette-Guérin (BCG) vaccinated site on the dorsum of the ear in guinea pigs. It is shown that whole cervical lymph node cells did not proliferate in vitro in the presence of soluble mycobacterial antigens (PPD or leprosin) despite being responsive to whole mycobacteria. Besides, T cells from these lymph nodes separated as a non-adherent fraction on a nylon wool column, proliferated to PPD in the presence of autologous antigen presenting cells. Interestingly, addition of as low as 20% nylon wool adherent cells to these, sharply decreased the proliferation by 83%. Looking into what cells in the adherent fraction suppressed the proliferation, it was found that neither the T cell nor the macrophage enriched cell fractions of this population individually showed suppressive effect, indicating that their co-presence was necessary for the suppression. Since BCG induced granulomas resolve much faster than granulomas induced by other mycobacteria such as Mycobacterium leprae the present experimental findings add to the existing evidence that intradermal BCG vaccination influences subsequent immune responses in the host and may further stress upon its beneficial role seen in Covid-19 patients.


Assuntos
Antígenos de Bactérias/farmacologia , Vacina BCG/farmacologia , Granuloma/imunologia , Linfonodos/imunologia , Linfócitos T/imunologia , Tuberculina/farmacologia , Animais , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/microbiologia , Adesão Celular , Proliferação de Células , Infecções por Coronavirus/prevenção & controle , Orelha , Feminino , Granuloma/microbiologia , Cobaias , Humanos , Injeções Intradérmicas , Linfonodos/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Mycobacterium bovis/imunologia , Mycobacterium leprae/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Remissão Espontânea , Linfócitos T/classificação , Linfócitos T/efeitos dos fármacos , Linfócitos T/microbiologia
3.
Vaccine ; 38(41): 6352-6356, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32863070

RESUMO

The world is facing the rising emergency of SARS-CoV-2. The outbreak of COVID-19 has caused a global public health and economic crisis.Recent epidemiological studies have shown that a possible association of BCG vaccination program with decreased COVID-19-related risks, suggesting that BCG may provide protection against COVID-19. Non-specific protection against viral infections is considered as a main mechanism of BCG and clinical trials to determine whether BCG vaccine can protect healthcare workers from the COVID-19 are currently underway. We hypothesized that BCG may carry similar T cell epitopes with SARS-CoV-2 and evaluated the hypothesis by utilizing publicly available database and computer algorithms predicting human leukocyte antigen (HLA) class I-binding peptides. We foundthatBCG contains similar 9-amino acid sequences with SARS-CoV-2. These closely-related peptides had moderate to high binding affinity for multiple common HLA class I molecules, suggesting that cross-reactive T cells against SARS-CoV-2 could be generated by BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos de Linfócito T/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Sequência de Aminoácidos/genética , Betacoronavirus/genética , Reações Cruzadas/imunologia , Epitopos de Linfócito T/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Vacinas Virais/imunologia
4.
Proc Natl Acad Sci U S A ; 117(34): 20848-20859, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32778586

RESUMO

Tuberculosis (TB) claims 1.5 million lives per year. This situation is largely due to the low efficacy of the only licensed TB vaccine, Bacillus Calmette-Guérin (BCG) against pulmonary TB. The metabolic disease type 2 diabetes (T2D) is a risk factor for TB and the mechanisms underlying increased TB susceptibility in T2D are not well understood. Furthermore, it is unknown if new TB vaccines will provide protection in the context of T2D. Here we used a diet-induced murine model of T2D to investigate the underlying mechanisms of TB/T2D comorbidity and to evaluate the protective capacity of two experimental TB vaccines in comparison to conventional BCG. Our data reveal a distinct immune dysfunction that is associated with diminished recognition of mycobacterial antigens in T2D. More importantly, we provide compelling evidence that mucosal delivery of recombinant BCG strains expressing the Mycobacterium tuberculosis (Mtb) ESX-1 secretion system (BCG::RD1 and BCG::RD1 ESAT-6 ∆92-95) are safe and confer superior immunity against aerosol Mtb infection in the context of T2D. Our findings suggest that the remarkable anti-TB immunity by these recombinant BCG strains is achieved via augmenting the numbers and functional capacity of antigen presenting cells in the lungs of diabetic mice.


Assuntos
Antígenos de Bactérias/farmacologia , Proteínas de Bactérias/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Animais , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Vacina BCG , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membrana Mucosa/imunologia , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinação
5.
J Proteome Res ; 19(11): 4649-4654, 2020 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-32794723

RESUMO

The Bacillus Calmette-Guerin vaccine is still widely used in the developing world. The vaccination prevents infant death not only from tuberculosis but also from unrelated infectious agents, especially respiratory tract infections and neonatal sepsis. It is proposed that these off-target protective effects of the BCG vaccine are mediated by the general long-term boosting of innate immune mechanisms, also termed "trained innate immunity". Recent studies indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs and encourage the initiation of several clinical studies with the expectation that revaccination with BCG could reduce the incidence and severity of COVID-19. Here, presented results from the bioinformatics analysis of the Mycobacterium bovis (strain BCG/Pasteur 1173P2) proteome suggests four immunodominant antigens that could induce an immune response against SARS-CoV-2.


Assuntos
Vacina BCG , Proteínas de Bactérias , Betacoronavirus , Infecções por Coronavirus , Reposicionamento de Medicamentos , Pandemias , Pneumonia Viral , Vacina BCG/química , Vacina BCG/imunologia , Proteínas de Bactérias/química , Proteínas de Bactérias/imunologia , Betacoronavirus/química , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Mycobacterium bovis/química , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Proteoma/química , Proteoma/imunologia , Vacinas Virais/química , Vacinas Virais/imunologia
6.
Mol Immunol ; 126: 101-109, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32795663

RESUMO

Autophagy is considered as an effective strategy for host cells to eliminate intracellular Mycobacterium tuberculosis (Mtb). Dual-specificity phosphatase 5 (DUSP5) is an endogenous phosphatase of ERK1/2, and plays an important role in host innate immune responses, its function in autophagy regulation however remains unexplored. In the present study, the function of DUSP5 in autophagy in Mycobacterium bovis Bacillus Calmette-Guerin (BCG)-infected RAW264.7 cells, a murine macrophage-like cell line, was examined by assessing the alteration of the cell morphology, expression of autophagy markers, and ERK1/2 signaling activation. The results demonstrated that the BCG infection could induce DUSP5 expression and activate ERK1/2 signaling in RAW264.7 cells; an activation of ERK1/2 signaling contributed to autophagic process in RAW264.7 cells. Moreover, DUSP5 knockdown increased the expression of autophagy-related proteins (Atgs), including LC3-II, Beclin1, Atg5 and Atg7. However, an overexpression of DUSP5 exhibited an opposite effect. Mechanistically, DUSP5 could inhibit the formation of autophagosome by suppressing the phosphorylation of signaling molecules in ERK1/2 signaling cascade. This study thus demonstrated a novel role of DUSP5 in modulating autophagy inRAW264.7 cells in response to BCG infection in particular, and autophagy macrophage to Mtb in general.


Assuntos
Autofagia/imunologia , Fosfatases de Especificidade Dupla/metabolismo , Sistema de Sinalização das MAP Quinases/imunologia , Mycobacterium bovis/imunologia , Tuberculose/imunologia , Animais , Autofagossomos/imunologia , Autofagossomos/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Modelos Animais de Doenças , Fosfatases de Especificidade Dupla/genética , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Fosforilação/genética , Fosforilação/imunologia , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Tuberculose/microbiologia
7.
Vaccine ; 38(41): 6374-6380, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32798142

RESUMO

The rapid spread of the Coronavirus pandemic and its significant health and social impact urges the search for effective and readily available solutions to mitigate the damages. Thus, evaluating the effectiveness of existing vaccines like Bacillus Calmette-Guérin (BCG) has attracted attention. The aim of this review was evidence synthesis on the effect of BCG vaccine in preventing severe infectious respiratory disease including COVD-19, but not tuberculosis. We considered studies conducted on human participants of any study design from any country setting that were published in Enlgish. We did a systematic literature search in MEDLINE, Scopus and Google scholar databases and a free search on Google. The identified studies were appraised and relevant data were extracted using Joanna Briggs Institute tools. The extracted findings were synthesized with tables and narrative summary. Nine studies met the inclusion criteria. The findings indicated that BCG vaccine has a strong protective effect against both upper and lower acute respiratory tract infections. For instance in countries with universal BCG vaccination policy, the incidence of COVID-19 was lower compared to the counterparts. Addtionally, BCG vaccine was found to protect against infections like lethal influenza A virus, pandemic influenza (H1N1), and other acute respiratory tract infections. BCG improved the human body's immune response involving antigen-specific T cells and memory cells. It also induced adaptive functional reprogramming of mononuclear phagocytes that induce protective effects against different respiratory infections other than tuberculosis. In countries with universal BCG vaccination, the incidence and death from acute respiratory viral infection including COVID - 19 is significantly low. However, there is an urgent need for further evidence from well-designed studies to understand the possible role of BCG vaccination over time and across age groups, its possible benefits in special populations such as health workers and cost-savings related to a policy of universal BCG vaccination.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Anticorpos Antivirais/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/prevenção & controle , Tuberculose Pulmonar/prevenção & controle , Vacinação
8.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
9.
mBio ; 11(3)2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561657

RESUMO

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Proteção Cruzada/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Atenuadas/imunologia , Ensaios Clínicos como Assunto , Infecções por Coronavirus/patologia , Humanos , Sarampo/imunologia , Caxumba/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/patologia , Rubéola (Sarampo Alemão)/imunologia , Vacinação
10.
J Appl Microbiol ; 129(5): 1207-1219, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32500542

RESUMO

AIMS: We employed a combination of diagnostic tests including single cervical tuberculin test (SCT), rapid lateral-flow test (RT), TB-Feron, conventional PCR and culture to investigate the prevalence of Mycobacterium bovis infections in dairy cattle under the intensive dairy production system in Egypt. METHODS AND RESULTS: In total, 2710 dairy cows from 11 herds in six Governorates were tested by SCT and 444 (16·4%) were TB reactors. Only 65 cows responded to M. bovis antigen by RT and TB-Feron. A postmortem examination showed that 49 (75·4%) of slaughtered cows have visible lesions. Testing of 215 out 444 SCT reactor cows by culture and PCR using blood and milk samples revealed that M. bovis were more frequently identified in the blood (6·1-20·5%) than milk (2·3-5·6%) samples. Additionally, in this study, we investigated the prevalence and potential risk factors associated with M. bovis infection in dairy farm workers. Overall, 100 dairy farm workers were tested using QuantiFERON-TB Gold In-Tube test to detect Mycobacterium tuberculosis complex (MTC) and 35 (35%) were positive. In all, 23 (23%) of MTC positive were M. bovis positive using PCR. Mycobacterium bovis positive cases were associated with workers who had respiratory signs and did not wash or disinfect their hands after handling cows. CONCLUSIONS: The prevalence of M. bovis in dairy cows and dairy farm workers under the intensive dairy production system in Egypt is high. It is therefore essential to disseminate effective prevention and control measures to prevent the spread of M. bovis between dairy cows and dairy workers. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the use of RT or TB-Feron as an ancillary test of SCT reactor cows resulted in a significant reduction in the SCT false-positive slaughtered cows. A high prevalence of M. bovis infection among farm workers provides evidence of occupational risk in the intensive dairy production system in Egypt.


Assuntos
Doenças dos Trabalhadores Agrícolas/diagnóstico , Indústria de Laticínios/estatística & dados numéricos , Fazendeiros/estatística & dados numéricos , Mycobacterium bovis/isolamento & purificação , Tuberculose Bovina/diagnóstico , Doenças dos Trabalhadores Agrícolas/epidemiologia , Doenças dos Trabalhadores Agrícolas/microbiologia , Animais , Bovinos , Egito/epidemiologia , Humanos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Saúde do Trabalhador , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/microbiologia , Tuberculose Bovina/transmissão
11.
EMBO Mol Med ; 12(6): e12661, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32379923

RESUMO

The ongoing severe acute respiratory sickness coronavirus 2 (SARS-CoV-2) pandemic has resulted in more than 3,600,000 detected cases of COVID-19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID-19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID-19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID-19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high-risk groups. COVID-19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID-19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.


Assuntos
Vacina BCG/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Mycobacterium bovis/genética , Mycobacterium bovis/imunologia , Mycobacterium bovis/metabolismo , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Risco , Sorogrupo , Análise de Sobrevida , Vacinação
12.
Medicine (Baltimore) ; 99(18): e19924, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358360

RESUMO

BACKGROUND: To investigate the efficacy and safety of acupoint injection of Bacillus Calmette-Guerin polysaccharide nucleic acid (BCG-PSN) in the treatment of chronic urticaria (CU). METHODS: The following databases will be searched from their inception: Medline, Embase, Pubmed, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure Database, China Biomedical Literature Database, China Science Journal Database, and Wanfang Database. All databases will be searched from the date of creation until October 2019. In addition, we will manually search the list of medical journals as a supplement. The scope of the search included randomized controlled clinical studies related to acupoint injection of BCG-PSN for CU. The primary outcome is the disease activity control. Secondary outcomes include response rate, adverse events, and recurrence rates. The Cochrane RevMan V5.3 Deviation Assessment Tool will be used to assess bias assessment risk, data integration risk, meta-analysis risk, and subgroup analysis risk (if conditions are met). The average difference, standard mean difference and binary data will be used to represent continuous results. RESULTS: This study will comprehensively review the existing evidence on the treatment of CU by acupoint injection of BCG-PSN. CONCLUSION: This systematic review will provide a judgment basis for the effectiveness and safety of acupoint injection of BCG-PSN in the treatment of CU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019139885.


Assuntos
Pontos de Acupuntura , Urticária Crônica/terapia , Medicina Tradicional Chinesa/métodos , Mycobacterium bovis/imunologia , Ácidos Nucleicos/uso terapêutico , Polissacarídeos Bacterianos/uso terapêutico , Humanos , Ácidos Nucleicos/administração & dosagem , Polissacarídeos Bacterianos/administração & dosagem , Recidiva , Projetos de Pesquisa
13.
PLoS Pathog ; 16(5): e1008356, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32437421

RESUMO

Tuberculosis (TB) is one of the deadliest diseases, claiming ~2 million deaths annually worldwide. The majority of people in TB endemic regions are vaccinated with Bacillus Calmette Guerin (BCG), which is the only usable vaccine available. BCG is efficacious against meningeal and disseminated TB in children, but protective responses are relatively short-lived and fail to protect against adult pulmonary TB. The longevity of vaccine efficacy critically depends on the magnitude of long-lasting central memory T (TCM) cells, a major source of which is stem cell-like memory T (TSM) cells. These TSM cells exhibit enhanced self-renewal capacity as well as to rapidly respond to antigen and generate protective poly-functional T cells producing IFN-γ, TNF-α, IL-2 and IL-17. It is now evident that T helper Th 1 and Th17 cells are essential for host protection against TB. Recent reports have indicated that Th17 cells preserve the molecular signature for TSM cells, which eventually differentiate into IFN-γ-producing effector cells. BCG is ineffective in inducing Th17 cell responses, which might explain its inadequate vaccine efficacy. Here, we show that revaccination with BCG along with clofazimine treatment promotes TSM differentiation, which continuously restores TCM and T effector memory (TEM) cells and drastically increases vaccine efficacy in BCG-primed animals. Analyses of these TSM cells revealed that they are predominantly precursors to host protective Th1 and Th17 cells. Taken together, these findings revealed that clofazimine treatment at the time of BCG revaccination provides superior host protection against TB by increasing long-lasting TSM cells.


Assuntos
Vacina BCG/imunologia , Vacina BCG/metabolismo , Clofazimina/farmacologia , Memória Imunológica/imunologia , Animais , Vacina BCG/farmacologia , Clofazimina/metabolismo , Quimioterapia Combinada/métodos , Feminino , Imunização Secundária/métodos , Imunogenicidade da Vacina/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Células-Tronco/imunologia , Células Th1/imunologia , Células Th17/imunologia , Tuberculose/imunologia , Tuberculose Pulmonar/imunologia
14.
Acta Biomed ; 91(2): 207-213, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32420947

RESUMO

Since the beginning of the COVID-19 epidemic, a possible explanation for the high heterogeneity of infection/mortality rates across involved countries was hinted in the prevalence of tuberculosis vaccination with Bacille Calmette-Guérin (BCG). A systematic review was therefore performed on May 2, 2020. A total of 13 articles were ultimately retrieved, 12 of them as preprint papers. All articles were ecological studies of low quality. Most of them did not include main confounding factors (i.e. demographic of the assessed countries, share of peo- ple residing in urban settings, etc.), and simply assessed the differences among incidence/mortality of COVID-19 with vaccination rates or by having vs. having not any vaccination policy for BCG. Even though all studies shared the very same information sources (i.e. international registries for BCG vaccination rates and open source data for COVID-19 epidemics), results were conflicting, with later studies apparently denying any true correlation between COVID-19 occurrence and BCG vaccination rates and/or policies. As a consequence, there is no sound evidence to recommend BCG vaccination for the prevention of COVID-19.


Assuntos
Vacina BCG/imunologia , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Mycobacterium bovis/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/imunologia , Humanos , Pneumonia Viral/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle
15.
Mem Inst Oswaldo Cruz ; 115: e190347, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428188

RESUMO

BACKGROUND Bacillus Calmette-Guérin (BCG) is considered a promising live bacterial delivery system. However, several proposals for rBCG vaccines have not progressed, mainly due to the limitations of the available expression systems. OBJECTIVES To obtain a set of mycobacterial vectors using a range of promoters with different strengths based on a standard backbone, previously shown to be stable. METHODS Mycobacterial expression vectors based on the pLA71 vector as backbone, were obtained inserting different promoters (PAN, PαAg, PHsp60, PBlaF* and PL5) and the green fluorescence protein (GFP) as reporter gene, to evaluate features such as their relative strengths, and the in vitro (inside macrophages) and in vivo stability. FINDINGS The relative fluorescence observed with the different vectors showed increasing strength of the promoters: PAN was the weakest in both Mycobacterium smegmatis and BCG and PBlaF* was higher than PHsp60 in BCG. The relative fluorescence observed in a macrophage cell line showed that PBlaF* and PHsp60 were comparable. It was not possible to obtain strains transformed with the extrachromosomal expression vector containing the PL5 in either species. MAIN CONCLUSION We have obtained a set of potentially stable mycobacterial vectors with a arrange of expression levels, to be used in the development of rBCG vaccines.


Assuntos
Vacina BCG/imunologia , Escherichia coli/imunologia , Vetores Genéticos/imunologia , Proteínas de Fluorescência Verde/imunologia , Mycobacterium bovis/imunologia , Mycobacterium smegmatis/imunologia , Animais , Escherichia coli/genética , Feminino , Vetores Genéticos/genética , Camundongos , Camundongos Endogâmicos BALB C
16.
Vet J ; 256: 105426, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32113584

RESUMO

Programs for the eradication of bovine tuberculosis (bTB) focus on the tuberculin skin test (TST) and slaughter of reactor cattle. However, the disease remains an animal health concern in several countries and improving the efficiency of the TST has become a critical issue. The detection of Mycobacterium bovis antibodies in serum, within weeks after the TST, may be a rapid and inexpensive way to improve bTB control. This study reports the validation of an enzyme-linked immunosorbent assay (ELISA) to detect bovine tuberculosis as an ancillary test to TST in dairy farms in Argentina. The estimated validation parameters were within the established requirements of the World Organization for Animal Health (OIE). The test demonstrated high repeatability, with coefficients of variation <25%. High test reproducibility through interlaboratory testing was also found, with an estimated Pearson coefficient of 0.9648 (95% confidence intervals 0.9315-0.9820). The ELISA detected tuberculous cattle unidentified by the TST. Of 43 animals sent to slaughterhouses that were ELISA positive 15-17 days after a negative TST, 36 were confirmed as infected with M. bovis by histopathology and IS6110 PCR. According to ROC curve analysis of results of 145 cattle from M. bovis-free herds and the 36 M. bovis-infected cattle, at a corrected optical density cut-off point of 0.3853, specificity was 95.95% and the positive predictive value at this cut-off was 83.72%. The ELISA detection test validated in this study could be readily applied in dairy farms, to complement a prior TST and improve livestock health.


Assuntos
Ensaio de Imunoadsorção Enzimática/veterinária , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Animais , Argentina , Bovinos , Indústria de Laticínios/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Reações Falso-Negativas , Feminino , Mycobacterium bovis/imunologia , Reprodutibilidade dos Testes , Teste Tuberculínico/métodos
17.
Comp Immunol Microbiol Infect Dis ; 69: 101424, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972498

RESUMO

Cattle, bison and buffaloes are susceptible to Mycobacterium bovis, the causative agent for bovine tuberculosis. Accurate and timely identification of infected animals is critical for improved management and control of disease in these species. Bovids develop humoral immune responses to M. bovis infection making serological tests attractive for tuberculosis screening. However, optimization and validation of antibody assays designed for various animal species require understanding of antigen recognition patterns in each target host. The objective of this study was to characterize serological reactivity profiles generated by cattle, American bison, and African buffaloes in tuberculosis. Serum samples from M. bovis-infected animals were tested for the presence of IgM and IgG antibodies to MPB70/MPB83 and CFP10/ESAT6 chimeric proteins using Dual-Path Platform technology. All three host species showed IgG responses of higher magnitude and frequency than IgM responses; further, IgM seroreactivity was limited to MPB70/MPB83, whereas IgG antibodies recognized both test antigens. In cattle, the IgM and IgG responses were elicited mainly by MPB70/MPB83, whereas bison and buffaloes showed similar IgG seroreactivity rates for MPB70/MPB83 and CFP10/ESAT6 antigens. The findings demonstrate distinct patterns of predominant antigen recognition by different bovid species in M. bovis infection.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Interações Hospedeiro-Patógeno/imunologia , Mycobacterium bovis/imunologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Imunoensaio , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia
18.
Res Vet Sci ; 129: 70-73, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31954316

RESUMO

Mycobacterium bovis is the cause of tuberculosis in most mammalian species, most notably cattle and other members of the family Bovidae; however, many species of the family Cervidae are also susceptible. In North America, tuberculosis has been identified in both captive and free-ranging cervids. Captive cervids are tested for tuberculosis following many of the same guidelines applied to cattle, including intradermal tuberculin testing using M. bovis purified protein derivative (PPD). Both captive and free-ranging deer and elk have been implicated as the source of infection for many cattle herds. Vaccination with the human vaccine M. bovis BCG has been considered as one possible tool to aid in eradication of tuberculosis from cattle and both captive and free-ranging cervids. Studies in cattle have demonstrated that BCG vaccination can induce false positive intradermal tuberculin test reactions in some cattle. Similar findings have been reported for red deer. We orally vaccinated white-tailed deer with BCG and showed that vaccination can induce false positive skin test reactions in some deer and that the rate of false positive reactions is greater with a higher vaccine dose.


Assuntos
Vacina BCG/imunologia , Cervos , Mycobacterium bovis/imunologia , Teste Tuberculínico/veterinária , Tuberculose/veterinária , Vacinação/veterinária , Animais , Tuberculose/prevenção & controle
19.
Transbound Emerg Dis ; 67(3): 1306-1314, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31899584

RESUMO

The present study highlights the transboundary nature of tuberculosis (TB) in alpacas and the failure of current antemortem testing protocols to identify TB-free alpaca herds and individuals for exportation. The tuberculin skin test (TST) failed to identify Mycobacterium bovis-infected animals prior to movement from the United Kingdom (UK) to Poland. This study describes the use of four serological assays [Enferplex Camelid TB, dual-path platform (DPP) VetTB and BovidTB assays, and multi-antigen print immunoassays (MAPIAs)] to detect TB in an alpaca herd with negative TST results. The breeding in Poland purchased alpacas for several years from the UK with the last group arriving in May 2018. In July 2018, two sick alpacas from the centre were hospitalized in a veterinary clinic and both died of TB a few weeks later. In November 2018, 20 alpacas remaining in this M. bovis-affected herd were euthanized and samples were collected. The study population included 20 M. bovis-infected and 20 uninfected alpacas, but only 15 infected animals were tested by all serology tests. The DPP VetTB and DPP BovidTB assays detected antibodies in 14 of the 20 infected alpacas, with results confirmed by MAPIA, and in none (MAPIA and DPP BovidTB) or one (DPP VetTB) of the 20 uninfected animals. None of the infected alpacas tested positive using the Enferplex assay. In addition, the group included three orphans and two cria-dam pairs, which provided an opportunity to analyse immune aspects of cria-mother relationships in this herd. The results suggest high susceptibility of this host species to M. bovis infection and rapid progression to disease. The serological tests used in this study offer useful tools for the detection of M. bovis infection in TST and Enferplex test non-reactive alpacas. These tests should be further evaluated for implementation into TB management and control strategies for camelid species.


Assuntos
Anticorpos Antibacterianos/sangue , Camelídeos Americanos , Mycobacterium bovis/imunologia , Testes Sorológicos/veterinária , Teste Tuberculínico/veterinária , Tuberculose/veterinária , Animais , Comércio , Reações Falso-Negativas , Polônia/epidemiologia , Testes Sorológicos/métodos , Tuberculose/microbiologia , Reino Unido/epidemiologia
20.
Mol Immunol ; 118: 73-78, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31855809

RESUMO

Host cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1ß, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.


Assuntos
2',5'-Oligoadenilato Sintetase/metabolismo , Nucleotídeos de Adenina/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Oligorribonucleotídeos/metabolismo , Tuberculose/metabolismo , 2',5'-Oligoadenilato Sintetase/imunologia , Nucleotídeos de Adenina/imunologia , Linhagem Celular , Citocinas/imunologia , Citoplasma/imunologia , Citoplasma/metabolismo , Citoplasma/microbiologia , Humanos , Inflamação/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Mycobacterium bovis/imunologia , Mycobacterium tuberculosis/imunologia , Oligorribonucleotídeos/imunologia , Células THP-1/imunologia , Células THP-1/metabolismo , Células THP-1/microbiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...