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1.
Gene ; 783: 145574, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33737124

RESUMO

Epidemiological and clinical evidence suggests that Bacille Calmette-Guérin (BCG) vaccine induced trained immunity protects against non-specific infections. Multiple clinical trials are currently underway to assess effectiveness of the vaccine in the coronavirus disease 2019 (COVID-19). However, the durability and mechanism of BCG trained immunity remain unclear. Here, an integrative analysis of available epidemiological transcriptomic data related to BCG vaccination and respiratory tract viral infections as well as of reported transcriptomic alterations in COVID-19 is presented toward addressing this gap. Results suggest that the vaccine induces very long-lasting transcriptomic changes that mimic viral infections by, consistent with the present concept of trained immunity, upregulation of antiviral defense response, and oppose viral infections by, inconsistent with the concept, downregulation of myeloid cell activation. These durability and mechanistic insights argue against possible indiscriminate use of the vaccine and activated innate immune response associated safety concerns in COVID-19, in that order.


Assuntos
Antivirais/uso terapêutico , Vacina BCG/uso terapêutico , Viroses/tratamento farmacológico , Adulto , Vacina BCG/imunologia , /imunologia , Criança , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Lactente , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Transcriptoma , Viroses/imunologia
2.
Front Immunol ; 12: 632478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763077

RESUMO

Despite of the rapid development of the vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it will take several months to have enough doses and the proper infrastructure to vaccinate a good proportion of the world population. In this interim, the accessibility to the Bacille Calmette-Guerin (BCG) may mitigate the pandemic impact in some countries and the BCG vaccine offers significant advantages and flexibility in the way clinical vaccines are administered. BCG vaccination is a highly cost-effective intervention against tuberculosis (TB) and many low-and lower-middle-income countries would likely have the infrastructure, and health care personnel sufficiently familiar with the conventional TB vaccine to mount full-scale efforts to administer novel BCG-based vaccine for COVID-19. This suggests the potential for BCG to overcome future barriers to vaccine roll-out in the countries where health systems are fragile and where the effects of this new coronavirus could be catastrophic. Many studies have reported cross-protective effects of the BCG vaccine toward non-tuberculosis related diseases. Mechanistically, this cross-protective effect of the BCG vaccine can be explained, in part, by trained immunity, a recently discovered program of innate immune memory, which is characterized by non-permanent epigenetic reprogramming of macrophages that leads to increased inflammatory cytokine production and consequently potent immune responses. In this review, we summarize recent work highlighting the potential use of BCG for the treatment respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials. In situations where no other specific prophylactic tools are available, the BCG vaccine could be used as a potential adjuvant, to decrease sickness of SARS-CoV-2 infection and/or to mitigate the effects of concurrent respiratory infections.


Assuntos
Vacina BCG/administração & dosagem , /imunologia , Animais , Vacina BCG/imunologia , /administração & dosagem , Humanos , Imunidade Inata , Pandemias , /fisiologia
3.
Epidemiol Infect ; 149: e75, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33722335

RESUMO

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.


Assuntos
/imunologia , Imunidade Inata/imunologia , Cobertura Vacinal/estatística & dados numéricos , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Assistência à Saúde/normas , Assistência à Saúde/estatística & dados numéricos , Humanos , Imunização Secundária/normas , Imunização Secundária/estatística & dados numéricos , Modelos Lineares , Vacina contra Sarampo/administração & dosagem , Vacina contra Sarampo/imunologia , Qualidade da Assistência à Saúde/normas , Qualidade da Assistência à Saúde/estatística & dados numéricos
4.
J Infect Dis ; 223(2): 189-191, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33535239

RESUMO

Developers of severe acute respiratory syndrome coronavirus 2 vaccines should consider some of the lessons from a "new" vaccine introduced in 1921, namely bacille Calmette-Guérin.


Assuntos
Vacina BCG/imunologia , /prevenção & controle , /imunologia , Animais , Vacina BCG/administração & dosagem , /virologia , Humanos , Pandemias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose/imunologia , Tuberculose/prevenção & controle
6.
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
7.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33468674

RESUMO

The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4 These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2.


Assuntos
Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/farmacologia , Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinas Conjugadas/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos de Bactérias/imunologia , Vacina BCG/imunologia , Vacina BCG/farmacologia , Proteínas de Bactérias , Linfócitos T CD4-Positivos/imunologia , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Receptor 2 Toll-Like/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinas Conjugadas/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/farmacologia
8.
Immunobiology ; 226(1): 152052, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418320

RESUMO

The century-old tuberculosis vaccine BCG has been the focus of renewed interest due to its well-documented ability to protect against various non-TB pathogens. Much of these broad spectrum protective effects are attributed to trained immunity, the epigenetic and metabolic reprogramming of innate immune cells. As BCG vaccine is safe, cheap, widely available, amendable to use as a recombinant vector, and immunogenic, it has immense potential for use as an immunotherapeutic agent for various conditions including autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infectious agents. Of particular interest is the use of BCG vaccination to counteract the increasing prevalence of autoimmune and allergic conditions in industrialized countries attributable to reduced infectious burden as described by the 'hygiene hypothesis.' Furthermore, BCG vaccination has been proposed as a potential therapy to mitigate spread and disease burden of COVID-19 as a bridge to development of a specific vaccine and recombinant BCG expression vectors may prove useful for the introduction of SARS-CoV-2 antigens (rBCG-SARS-CoV-2) to induce long-term immunity. Understanding the immunomodulatory effects of BCG vaccine in these disease contexts is therefore critical. To that end, we review here BCG-induced immunomodulation focusing specifically on BCG-induced trained immunity and how it relates to the 'hygiene hypothesis' and COVID-19.


Assuntos
Vacina BCG/imunologia , Vacina BCG/uso terapêutico , /terapia , Hipótese da Higiene , Imunidade Inata , /virologia , Humanos , Imunomodulação
9.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466825

RESUMO

Dilated cardiomyopathy (DCM) is a potentially lethal disorder characterized by progressive impairment of cardiac function. Chronic myocarditis has long been hypothesized to be one of the causes of DCM. However, owing to the lack of suitable animal models of chronic myocarditis, its pathophysiology remains unclear. Here, we report a novel mouse model of chronic myocarditis induced by recombinant bacille Calmette-Guérin (rBCG) expressing a CD4+ T-cell epitope of cardiac myosin heavy chain-α (rBCG-MyHCα). Mice immunized with rBCG-MyHCα developed chronic myocarditis, and echocardiography revealed dilation and impaired contraction of ventricles, similar to those observed in human DCM. In the heart, CD62L-CD4+ T cells were increased and produced significant amounts of IFN-γ and IL-17 in response to cardiac myosin. Adoptive transfer of CD62L-CD4+ T cells induced myocarditis in the recipient mice, which indicated that CD62L-CD4+ T cells were the effector cells in this model. rBCG-MyHCα-infected dendritic cells produced proinflammatory cytokines and induced MyHCα-specific T-cell proliferation and Th1 and Th17 polarization. This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.


Assuntos
Vacina BCG/imunologia , Modelos Animais de Doenças , Epitopos de Linfócito T/imunologia , Miocardite/imunologia , Miosinas Ventriculares/imunologia , Animais , Vacina BCG/genética , Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/fisiopatologia , Doença Crônica , Citocinas/imunologia , Citocinas/metabolismo , Ecocardiografia , Epitopos de Linfócito T/genética , Humanos , Interleucina-17/imunologia , Interleucina-17/metabolismo , Ativação Linfocitária , Masculino , Camundongos Endogâmicos BALB C , Miocardite/patologia , Miocardite/fisiopatologia , Proteínas Recombinantes/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Miosinas Ventriculares/genética
10.
Ned Tijdschr Geneeskd ; 1642020 10 07.
Artigo em Holandês | MEDLINE | ID: mdl-33331729

RESUMO

A number of clinical trials are currently underway worldwide to assess whether BCG, the old vaccine against tuberculosis, can protect against COVID-19 infection. In this Perspective, we briefly outline the background, the immunological mechanisms (in particular induction of 'innate immune memory' or 'trained immunity'), and further considerations for the potential future use of BCG against viral and other infections.


Assuntos
Vacina BCG , Reposicionamento de Medicamentos/métodos , Memória Imunológica/imunologia , Tuberculose/prevenção & controle , Vacina BCG/imunologia , Vacina BCG/uso terapêutico , /prevenção & controle , Humanos , Imunidade Inata/imunologia , Tuberculose/imunologia
11.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-47940

RESUMO

A Fiocruz inicia, nesta segunda-feira (19/10), o Brace Trial Brasil (BTB), estudo com a vacina BCG que visa reduzir o impacto do Covid-19 em trabalhadores de saúde. O recrutamento dos voluntários será realizado na Faculdade de Medicina da Universidade Federal do Mato Grosso do Sul (UFMS) e os interessados devem realizar pré-cadastro pela internet.


Assuntos
Infecções por Coronavirus , Vacina BCG/imunologia , Pesquisa
12.
Front Immunol ; 11: 2059, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013871

RESUMO

The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends."


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Imunidade Inata , Memória Imunológica/imunologia , Pneumonia Viral/imunologia , Vacinação , Idoso , Animais , Vacinas Anticâncer/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Humanos , Micobactérias não Tuberculosas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/virologia , Risco , Vacinas Virais/efeitos adversos
13.
Pharm Res ; 37(11): 212, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33025261

RESUMO

PURPOSE: Coronavirus disease 2019 (COVID-19) is expected to continue to cause worldwide fatalities until the World population develops 'herd immunity', or until a vaccine is developed and used as a prevention. Meanwhile, there is an urgent need to identify alternative means of antiviral defense. Bacillus Calmette-Guérin (BCG) vaccine that has been recognized for its off-target beneficial effects on the immune system can be exploited to boast immunity and protect from emerging novel viruses. METHODS: We developed and employed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and affect a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. RESULTS: Our analysis demonstrates that BCG vaccine affects the production and maturation of naïve T cells resulting in enhanced, long-lasting trained innate immune responses that can provide protection against novel viruses. We have identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, our top hits emetine and lopinavir were independently validated by recent experimental findings that these compounds inhibit the growth of SARS-CoV-2 in vitro. CONCLUSIONS: Our results provide systems biology support for using BCG and small-molecule BCG mimics as putative vaccine and drug candidates against emergent viruses including SARS-CoV-2.


Assuntos
Vacina BCG/administração & dosagem , Materiais Biomiméticos/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Reposicionamento de Medicamentos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Bibliotecas de Moléculas Pequenas/administração & dosagem , Vacinas Virais/administração & dosagem , Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Humanos , Imunidade Inata , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Biologia de Sistemas/métodos , Vacinas Virais/imunologia , Fluxo de Trabalho
14.
Nat Commun ; 11(1): 5225, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067434

RESUMO

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from Cxcr3-/- mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Animais , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Cobaias , Humanos , Masculino , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Tuberculose/etiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/prevenção & controle
15.
PLoS Pathog ; 16(10): e1008969, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33119725

RESUMO

Protective variables for Coronavirus Disease 2019 (COVID-19) are unknown. "Trained immunity" of the populace as a result of Bacille Calmette-Guérin (BCG) vaccination policy implementation and coverage had been suggested to be one of the factors responsible for the differential impact of COVID-19 on different countries. Several trials are underway to evaluate the potential protective role of BCG vaccination in COVID-19. However, the lack of clarity on the use of appropriate controls concerning the measures of "trained immunity" or the heterologous cell-mediated immunity conferred by BCG vaccination has been a cause of concern leading to more confusion as exemplified by a recently concluded trial in Israel that failed to find any protective correlation with regard to BCG vaccination. Whereas, when we analyze the COVID-19 epidemiological data of European countries without any regard for BCG vaccination policy but with similar age distribution, comparable confounding variables, and the stage of the pandemic, the prevalence of tuberculin immunoreactivity-a measure of cell-mediated immunity persistence as a result of Mycobacterium spp. (including BCG vaccine) exposure of the populations-is found consistently negatively correlated with COVID-19 infections and mortality. We seek to draw attention toward the inclusion of controls for underlying "trained immunity" and heterologous cell-mediated immunity prevalence that may be preexisting or resulting from the intervention (e.g., BCG vaccine) in such trials to arrive at more dependable conclusions concerning potential benefit from them.


Assuntos
Vacina BCG/imunologia , Infecções por Coronavirus/imunologia , Imunidade Celular , Mycobacterium/imunologia , Pneumonia Viral/imunologia , Vacinação , Betacoronavirus , Humanos , Pandemias
16.
Allergol. immunopatol ; 48(5): 507-517, sept.-oct. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-191234

RESUMO

The impact of COVID-19 is changing with country wise and depend on universal immunization policies. COVID-19 badly affects countries that did not have universal immunization policies or having them only for the selective population of countries (highly prominent population) like Italy, USA, UK, Netherland, etc. Universal immunization of BCG can provide great protection against the COVID-19 infection because the BCG vaccine gives broad protection against respiratory infections. BCG vaccine induces expressions of the gene that are involved in the antiviral innate immune response against viral infections with long-term maintenance of BCG vaccine-induced cellular immunity. COVID-19 cases are reported very much less in the countries with universal BCG vaccination policies such as India, Afghanistan, Nepal, Bhutan, Bangladesh, Israel, Japan, etc. as compared to without BCG implemented countries such as the USA, Italy, Spain, Canada, UK, etc. BCG vaccine provides protection for 50-60 years of immunization, so the elderly population needs to be revaccinated with BCG. Several countries started clinical trials of the BCG vaccine for health care workers and elderly people. BCG can be uses as a prophylactic treatment until the availability of the COVID-19 vaccine


No disponible


Assuntos
Humanos , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/imunologia , Pandemias , Vacina BCG/imunologia
17.
PLoS Pathog ; 16(9): e1008887, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956412

RESUMO

Despite the availability of multiple antibiotics, tuberculosis (TB) remains a major health problem worldwide, with one third of the population latently infected and ~2 million deaths annually. The only available vaccine for TB, Bacillus Calmette Guérin (BCG), is ineffective against adult pulmonary TB. Therefore, alternate strategies that enhance vaccine efficacy are urgently needed. Vaccine efficacy and long-term immune memory are critically dependent on central memory T (TCM) cells, whereas effector memory T (TEM) cells are important for clearing acute infections. Recently, it has been shown that inhibition of the Kv1.3 K+ ion channel, which is predominantly expressed on TEM but not TCM cells, profoundly enhances TCM cell differentiation. We exploited this phenomenon to improve TCM:TEM cell ratios and protective immunity against Mycobacterium tuberculosis infection in response to BCG vaccination of mice. We demonstrate that luteolin, a plant-derived Kv1.3 K+ channel inhibitor, profoundly promotes TCM cells by selectively inhibiting TEM cells, and significantly enhances BCG vaccine efficacy. Thus, addition of luteolin to BCG vaccination may provide a sustainable means to improve vaccine efficacy by boosting host immunity via modulation of memory T cell differentiation.


Assuntos
Vacina BCG/imunologia , Memória Imunológica/efeitos dos fármacos , Canal de Potássio Kv1.3 , Luteolina/farmacologia , Mycobacterium tuberculosis/imunologia , Linfócitos T/imunologia , Tuberculose/imunologia , Animais , Canal de Potássio Kv1.3/antagonistas & inibidores , Canal de Potássio Kv1.3/imunologia , Camundongos , Tuberculose/prevenção & controle
18.
Cell ; 183(2): 315-323.e9, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32941801

RESUMO

BCG vaccination in children protects against heterologous infections and improves survival independently of tuberculosis prevention. The phase III ACTIVATE trial assessed whether BCG has similar effects in the elderly. In this double-blind, randomized trial, elderly patients (n = 198) received BCG or placebo vaccine at hospital discharge and were followed for 12 months for new infections. At interim analysis, BCG vaccination significantly increased the time to first infection (median 16 weeks compared to 11 weeks after placebo). The incidence of new infections was 42.3% (95% CIs 31.9%-53.4%) after placebo vaccination and 25.0% (95% CIs 16.4%-36.1%) after BCG vaccination; most of the protection was against respiratory tract infections of probable viral origin (hazard ratio 0.21, p = 0.013). No difference in the frequency of adverse effects was found. Data show that BCG vaccination is safe and can protect the elderly against infections. Larger studies are needed to assess protection against respiratory infections, including COVID-19 (ClinicalTrials.gov NCT03296423).


Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Infecções Respiratórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Vacina BCG/administração & dosagem , Método Duplo-Cego , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/imunologia , Viroses/imunologia , Viroses/prevenção & controle
19.
BMC Infect Dis ; 20(1): 677, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942991

RESUMO

BACKGROUND: Approximately 80% - 90% of individuals infected with latent Mycobacterium tuberculosis (Mtb) remain protected throughout their life-span. The release of unique, latent-phase antigens are known to have a protective role in the immune response against Mtb. Although the BCG vaccine has been administered for nine decades to provide immunity against Mtb, the number of TB cases continues to rise, thereby raising doubts on BCG vaccine efficacy. The shortcomings of BCG have been associated with inadequate processing and presentation of its antigens, an inability to optimally activate T cells against Mtb, and generation of regulatory T cells. Furthermore, BCG vaccination lacks the ability to eliminate latent Mtb infection. With these facts in mind, we selected six immunodominant CD4 and CD8 T cell epitopes of Mtb expressed during latent, acute, and chronic stages of infection and engineered a multi-epitope-based DNA vaccine (C6). RESULT: BALB/c mice vaccinated with the C6 construct along with a BCG vaccine exhibited an expansion of both CD4 and CD8 T cell memory populations and augmented IFN-γ and TNF-α cytokine release. Furthermore, enhancement of dendritic cell and macrophage activation was noted. Consequently, illustrating the elicitation of immunity that helps in the protection against Mtb infection; which was evident by a significant reduction in the Mtb burden in the lungs and spleen of C6 + BCG administered animals. CONCLUSION: Overall, the results suggest that a C6 + BCG vaccination approach may serve as an effective vaccination strategy in future attempts to control TB.


Assuntos
Vacina BCG/imunologia , Epitopos de Linfócito T , Tuberculose/prevenção & controle , Vacinas de DNA/imunologia , Animais , Antígenos de Bactérias/imunologia , Vacina BCG/genética , Vacina BCG/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/genética , Feminino , Memória Imunológica , Interferon gama/metabolismo , Tuberculose Latente/prevenção & controle , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Vacinas de DNA/farmacologia
20.
Sci Adv ; 6(32): eabc1463, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32923613

RESUMO

Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of a range of infectious diseases, and if so, it could protect against coronavirus disease 2019 (COVID-19). Here, we compared countries that mandated BCG vaccination until at least 2000 with countries that did not. To minimize any systematic effects of reporting biases, we analyzed the rate of the day-by-day increase in both confirmed cases (134 countries) and deaths (135 countries) in the first 30-day period of country-wise outbreaks. The 30-day window was adjusted to begin at the country-wise onset of the pandemic. Linear mixed models revealed a significant effect of mandated BCG policies on the growth rate of both cases and deaths after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions (e.g., individualism). Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.


Assuntos
Vacina BCG/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/transmissão , Saúde Pública/legislação & jurisprudência , Vacinação/estatística & dados numéricos
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