BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny

Vaccines have been traditionally developed with the presumption that they exert identical immunogenicity regardless of target population and that they provide protection solely against their target pathogen. However, it is increasingly appreciated that vaccines can have off-target effects and that vaccine immunogenicity can vary substantially with demographic factors such as age and sex. Bacille Calmette-Guérin (BCG), the live attenuated Mycobacterium bovis vaccine against tuberculosis (TB), represents a key example of these concepts. BCG vaccines are manufactured under different conditions across the globe generating divergent formulations. Epidemiologic studies have linked early life immunization with certain BCG formulations to an unanticipated reduction (∼50%) in all-cause mortality, especially in low birthweight males, greatly exceeding that attributable to TB prevention. This mortality benefit has been related to prevention of sepsis and respiratory infections suggesting that BCG induces “heterologous” protection against unrelated pathogens. Proposed mechanisms for heterologous protection include vaccine-induced immunometabolic shifts, epigenetic reprogramming of innate cell populations, and modulation of hematopoietic stem cell progenitors resulting in altered responses to subsequent stimuli, a phenomenon termed “trained immunity.” In addition to genetic differences, licensed BCG formulations differ markedly in content of viable mycob...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research

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CONCLUSIONS: The average patient is middle aged (often male) with a history of subacute back pain, sometimes presenting fever and/or neurological damage on diagnosis. Acute phase reactants are frequently raised. Diabetes mellitus, endocarditis and immunosuppressed patients may have the worst chance of a good outcome, therefore these patients should be more carefully managed (always try to obtain an imaging-guided biopsy, correct antibiotic treatment, and a functional and clinical follow-up). PMID: 32446680 [PubMed - as supplied by publisher]
Source: Medicina Clinica - Category: General Medicine Tags: Med Clin (Barc) Source Type: research
Both hair graying and hair loss with age are well researched topics, but there remains considerable uncertainty over which of the possible mechanisms involved are the most relevant, or most useful as targets for therapy. This state of affairs is well illustrated by the feverish interest that attends any possible advance towards reversing male and female pattern baldness. Also the sizable marketplaces devoted to treatments that work poorly, if at all. Today's trial results are interesting, in that I don't recall seeing stem cell factors being used topically before. There is of course a great deal of nonsense and unsc...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Publication date: Available online 24 May 2020Source: Neurología (English Edition)Author(s): M. León Ruiz, M. Sospedra, S. Arce Arce, J. Tejeiro-Martínez, J. Benito-León
Source: Neurologia - Category: Neurology Source Type: research
Publication date: Available online 24 May 2020Source: Neurología (English Edition)Author(s): A.I. Pérez-Álvarez, P. Suárez-Santos, M. González-Delgado, P. Oliva-Nacarino
Source: Neurologia - Category: Neurology Source Type: research
Publication date: Available online 25 May 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Charmaine Yam, Daniel Merlo, Jim Stankovich, David Darby, Melissa Gresle, Tomas Kalincik, Trevor J Kilpatrick, Jeanette Lechner-Scott, Bruce Taylor, Michael Barnett, Helmut Butzkueven, Anneke van der Walt
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 24 May 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Thomas Mathew, Ms Saji K John, Vikram Kamath, Uday Murgod, Kurian Thomas, Anita Angela Baptist, Manjusha Therambil, Asha Shaji, Raghunandan Nadig, Sagar Badachi, Delon D Souza, Sonia Shivde, Amrutha Avati, G R K Sarma, G G Sharath Kumar, Saikanth Deepalam, Gareth J Parry
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 24 May 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Magdalena Zoledziewska
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
TYPE 2 diabetes does not pose a threat if you keep blood sugar levels under control. Diet acts as the ultimate bulwark against high blood sugar levels and a natural green powder has been proven to lower blood sugar.
Source: Daily Express - Health - Category: Consumer Health News Source Type: news
Publication date: Available online 24 May 2020Source: Canadian Journal of DiabetesAuthor(s): Jacob M. Zamora, Jason M. Kong
Source: Canadian Journal of Diabetes - Category: Endocrinology Source Type: research
CD4+ T-Cells With High Common γ Chain Expression and Disturbed Cytokine Production Are Enriched in Children With Type-1 Diabetes Julia Seyfarth1*, Nathalie Mütze1, Jennifer Antony Cruz1, Sebastian Kummer1, Christina Reinauer1, Ertan Mayatepek1, Thomas Meissner1,2 and Marc Jacobsen1 1Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital, Medical Faculty, Düsseldorf, Germany 2German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany The common gamma chain (γc) contributes to the formation of different c...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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