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

Tuberculosis (TB) remains a major health threat. Although a vaccine has been available for almost 100 years termed Bacille Calmette-Guérin (BCG), it is insufficient and better vaccines are urgently needed. This treatise describes first the basic immunology and pathology of TB with an emphasis on the role of T lymphocytes. Better understanding of the immune response to Mycobacterium tuberculosis (Mtb) serves as blueprint for rational design of TB vaccines. Then, disease epidemiology and the benefits and failures of BCG vaccination will be presented. Next, types of novel vaccine candidates are being discussed. These include: (i) antigen/adjuvant subunit vaccines; (ii) viral vectored vaccines; and (III) whole cell mycobacterial vaccines which come as live recombinant vaccines or as dead whole cell or multi-component vaccines. Subsequently, the major endpoints of clinical trials as well as administration schemes are being described. Major endpoints for clinical trials are prevention of infection (PoI), prevention of disease (PoD), and prevention of recurrence (PoR). Vaccines can be administered either pre-exposure or post-exposure with Mtb. A central part of this treatise is the description of the viable BCG-based vaccine, VPM1002, currently undergoing phase III clinical trial assessment. Finally, new approaches which could facilitate design of refined next generation TB vaccines will be discussed.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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[UCT] Researchers from the South African Tuberculosis Vaccine Initiative (SATVI) at the University of Cape Town (UCT), the Center for Global Infectious Disease Research - Seattle in the United States, and a large consortium of collaborators have developed a validated a new, simple blood-based test that has the potential to serve multiple functions in the fight against TB.
Source: AllAfrica News: Tuberculosis - Category: Infectious Diseases Source Type: news
Buruli ulcer (BU) is a neglected, tropical infectious disease of the skin and the subcutaneous tissue caused by Mycobacterium ulcerans. This pathogen has emerged as a new species from a common ancestor with Mycobacterium marinum by acquisition of the virulence plasmid pMUM. The plasmid encodes enzymes required for the synthesis of the macrolide toxin mycolactone, which has cytotoxic and immunosuppressive activities. In advanced BU lesions, extracellular clusters of M. ulcerans reside in necrotic subcutaneous tissue and are protected from infiltrating leukocytes by the cytotoxic activity of secreted mycolactone. Several lin...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we examine the effect of intradermal vaccination with Mycobacterium bovis bacille Calmette-Guèrin on macrophage phenotype following intranasal challenge with virulent Mycobacterium bovis. Preserved lung tissues used in the present study were obtained from a previous vaccination trial in BALB/c mice. Vaccinated mice showed less extensive pulmonary lesions along with a significant decrease in bacterial lung burden when compared to control mice. Immunohistochemical markers of classically activated macrophages (iNOS) and alternatively activated macrophages (Arg1, FIZZ1) were applied to lung sections. Vacc...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
The generation of enduring protective immunity by vaccines is of utmost importance. Intriguingly, there is considerable variation in the efficacy of vaccines amongst individuals. Various studies have shown that normal flora of gastrointestinal tract plays a vital role in maintaining host homeostasis and immunity. Since gut microbiome is also extremely variable between individuals, we speculate that it might impact individual’s response to vaccines. Consequently, we administered broad spectrum antibiotics cocktail to induce gut dysbiosis and monitored its impact on the generation of long-lasting memory T cells and the...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Here’s betting you wouldn’t want anyone blowing smallpox scabs up your nose. But you might feel differently if you lived in 15th century China. Long ago, the Chinese recognized that people who had contracted smallpox once were immune to reinfection. They came up with the idea of preserving scabs from individuals who had suffered mild cases, drying them out, crushing them to a powder and blowing them up the nostril. For boys it was the right nostril, for girls it was the left because, well, 15th century. That is how the story of vaccines usually begins, though that version is decidedly incomplete. For one thing,...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized COVID-19 Explainer health Source Type: news
[IPS] This week, the Bill and Melinda Gates Foundation announced it will donate A$10 million to help fund an Australian trial testing whether a very old vaccine, BCG, can be used against a new threat, COVID-19. So what is the BCG vaccine and what might its place be in the fight against coronavirus?
Source: AllAfrica News: Tuberculosis - Category: Infectious Diseases Source Type: news
This article is republished from The Conversation under a Creative Commons license. Read the original article. The post Could BCG, a 100-year-old Vaccine for Tuberculosis, Protect Against Coronavirus? appeared first on Inter Press Service.
Source: IPS Inter Press Service - Health - Category: International Medicine & Public Health Authors: Tags: Global Headlines Health Source Type: news
Conclusions: Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We report on the safety of the Polish (Moreau strain) “Bacille Calmete-Guerin-10” vaccine in an Australian cohort. Using active surveillance, we identified an adverse event rate of 54.6 per 10,000 doses (95% confidence interval: 38.5–75.2), which was comparable to that reported with the Danish Sanofi-Pasteur and Connaught strains.
Source: The Pediatric Infectious Disease Journal - Category: Infectious Diseases Tags: Vaccine Reports Source Type: research
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 ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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