Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology

Kaufmann, Stefan H. E.

doi:10.3389/fimmu.2020.00316

Cited by 65 publications

(77 citation statements)

References 131 publications

(183 reference statements)

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“…These deletions alter the expression of different Mycobacterium virulence factors (18)(19)(20)(21). The differential expression of these molecules leads to the induction of different immune responses when exposed to an M. tuberculosis infection or BCG vaccination (8,22). Trained immunity induction has only been described for BCG vaccination (13)(14)(15)23).…”

Section: Introductionmentioning

confidence: 99%

Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

et al. 2020

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Trained immunity is a type of non-specific memory-like immune response induced by some pathogens and vaccines, such as BCG, which can confer antigen-independent protection against a wide variety of pathogens. The BCG vaccine has been extensively used to protect against tuberculosis for almost a 100 years. Interestingly, this vaccine reduces children's mortality caused by infections unrelated to Mycobacterium tuberculosis infection, a phenomenon thought to be due to the induction of trained immunity. The SARS-CoV-2 pandemic has infected, as of April 22, 2020, 2,623,231 people globally, causing a major public health problem worldwide. Currently, no vaccine or treatment is available to control this pandemic. We analyzed the number of positive cases and deaths in different countries and correlated them with the inclusion of BCG vaccination at birth in their national vaccination programs. Interestingly, those countries where BCG vaccination is given at birth have shown a lower contagion rate and fewer COVID-19-related deaths, suggesting that this vaccine may induce trained immunity that could confer some protection for SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

et al. 2020

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“…The development of newer vaccines aims at either a new form of recombinant BCG (rBCG) or ones that boosts the conventional BCG vaccine. Several potential rBCG/BCG vaccine candidates with novel adjuvants are currently being evaluated for use in TB prevention in clinical studies [139][140][141][142]. As previously stated, studies using mouse models have indicated the cross-reactive immunity offered by BCG to pulmonary NTM infections caused by M. avium, M. abscessus, and M. kansasii [82,143].…”

Section: Complications Of Ntm Disease Treatmentmentioning

confidence: 95%

Of tuberculosis and non-tuberculous mycobacterial infections – a comparative analysis of epidemiology, diagnosis and treatment

et al. 2020

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Pulmonary diseases due to mycobacteria cause significant morbidity and mortality to human health. In addition to tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), recent epidemiological studies have shown the emergence of non-tuberculous mycobacteria (NTM) species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only a handful, primarily Mycobacterium avium complex and M. abscessus, have been implicated in pulmonary disease. While TB is transmitted through inhalation of aerosol droplets containing Mtb, generated by patients with symptomatic disease, NTM disease is mostly disseminated through aerosols originated from the environment. However, following inhalation, both Mtb and NTM are phagocytosed by alveolar macrophages in the lungs. Subsequently, various immune cells are recruited from the circulation to the site of infection, which leads to granuloma formation. Although the pathophysiology of TB and NTM diseases share several fundamental cellular and molecular events, the host-susceptibility to Mtb and NTM infections are different. Striking differences also exist in the disease presentation between TB and NTM cases. While NTM disease is primarily associated with bronchiectasis, this condition is rarely a predisposing factor for TB. Similarly, in Human Immunodeficiency Virus (HIV)-infected individuals, NTM disease presents as disseminated, extrapulmonary form rather than as a miliary, pulmonary disease, which is seen in Mtb infection. The diagnostic modalities for TB, including molecular diagnosis and drug-susceptibility testing (DST), are more advanced and possess a higher rate of sensitivity and specificity, compared to the tools available for NTM infections. In general, drugsensitive TB is effectively treated with a standard multi-drug regimen containing well-defined first-and second-line antibiotics. However, the treatment of drug-resistant TB requires the additional, newer class of antibiotics in combination with or without the first and second-line drugs. In contrast, the NTM species display significant heterogeneity in their susceptibility to standard anti-TB drugs. Thus, the treatment for NTM diseases usually involves the use of macrolides and injectable aminoglycosides. Although well-established international guidelines are available, treatment of NTM disease is mostly empirical and not entirely

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“…Weiner Kaufmann, 2020Ag85A, PPE, and pfkB Multistage DNA vaccine, A39 Su et al, 2017Ag85C, MPT5, and HspX rBCG-CMX da Costa et al, 2017 Lipo-AE vaccine formulation with the PolyIC adjuvant Diogo et al, 2019 ESAT-6, CFP-10, TB10.3, AlaDH, Ag85B, PstS1, andHspX ELISPOT assay Chiappini et al, 2012 38kD, ESAT-6, and CFP-10 Multiple-antigen detection assay Dai et al, 2017 CFP-10 and ESAT-6 Electrochemical-based SPCE Bakhori et al, 2020 ESAT-6, 6-kDa early secretory antigenic target; CFP, culture filtrate protein; rBCG, recombinant bacille Calmette-Guérin; ELISPOT, enzyme-linked immunospot assay; CMX, Ag85C-MPT51-HspX fusion protein; SPCE, screen-printed carbon electrode. For further details on Mycobacterium tuberculosis (Mtb) proteins, see the database: http://www.tbdb.org and http://tuberculist.epfl.ch immune response to the Ag85B antigen, but a weak immune response to ESAT-6 (Diogo et al, 2019).…”

Section: Id93mentioning

confidence: 99%

“…In LTBI, the Mtb reproduces inside the cellular host, developing a complex relationship that might progress to active TB infection (ATBI). Because TB is one of the top 10 causes of death from an infectious agent, prevention strategies and the development of better vaccines have been pursued (Kaufmann, 2020). Also, about 2000 million people worldwide have LTBI that might progress to ATBI at any time .…”

Section: Introductionmentioning

confidence: 99%

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Application of antigenic biomarkers for Mycobacterium tuberculosis

Rodríguez-Hernández

Quintas-Granados

Flores-Villalva

et al. 2020

J. Zhejiang Univ. Sci. B

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The study and characterization of biomolecules involved in the interaction between mycobacteria and their hosts are crucial to determine their roles in the invasion process and provide basic knowledge about the biology and pathogenesis of disease. Promising new biomarkers for diagnosis and immunotherapy have emerged recently. My-cobacterium is an ancient pathogen that has developed complex strategies for its persistence in the host and environment, likely based on the complexity of the network of interactions between the molecules involved in infection. Several biomarkers have received recent attention in the process of developing rapid and reliable detection techniques for tuberculosis. Among the most widely investigated antigens are CFP-10 (10-kDa culture filtrate protein), ESAT-6 (6-kDa early secretory antigenic target), Ag85A, Ag85B, CFP-7, and PPE18. Some of these antigens have been proposed as biomarkers to assess the key elements of the response to infection of both the pathogen and host. The design of novel and accurate diagnostic methods is essential for the control of tuberculosis worldwide. Presently, the diagnostic methods are based on the identification of molecules in the humoral response in infected individuals. Therefore, these tests depend on the capacity of the host to develop an immune response, which usually is heterogeneous. In the last 20 years, special attention has been given to the design of multiantigenic diagnostic methods to improve the levels of sensitivity and specificity. In this review, we summarize the state of the art in the study and use of mycobacterium biomolecules with the potential to support novel tuberculosis control strategies.

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Vaccination Against Tuberculosis: Revamping BCG by Molecular Genetics Guided by Immunology

Cited by 65 publications

References 131 publications

Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

Of tuberculosis and non-tuberculous mycobacterial infections – a comparative analysis of epidemiology, diagnosis and treatment

Application of antigenic biomarkers for Mycobacterium tuberculosis

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