The Worst Outbreaks in U.S. History

tuberculosis vaccine :: Article Creator

Oxford University Launches A Study Into Inhaled TB Vaccine

Beta Terms By using the Beta Site, you agree that such use is at your own risk and you know that the Beta Site may include known or unknown bugs or errors, that we have no obligation to make this Beta Site available with or without charge for any period of time, nor to make it available at all, and that nothing in these Beta Terms or your use of the Beta Site creates any employment relationship between you and us. The Beta Site is provided on an "as is" and "as available" basis and we make no warranty to you of any kind, express or implied.

In case of conflict between these Beta Terms and the BBC Terms of Use these Beta Terms shall prevail.

Letter: Congress Needs To Take Action On READ, End TB Now Acts

To the Editor:

Breaking news: Congress adjourned without passing important legislation. OK, so that's not unusual at all. Left hanging are two pieces of foreign policy really deserve attention.

Education is the foundation of healthy families, a more prosperous future, and good governance. Yet according to a new UNESCO report, 250 million children were out of school in 2022, six million more than the previous year. The READ Act Reauthorization would mitigate this crisis by continuing proven policies that build strong partnerships and deliver results, particularly for girls and young people in conflict-ridden nations. The READ Act Reauthorization unanimously passed the Senate in November. House leaders should follow their lead and pass HR681.

We hear a lot about COVID, flu and RSV. But a different disease, tuberculosis, killed 1.6 million people in 2021. Most of the 10.5 million new cases last year were in low and middle-income countries. But, airborne like COVID, TB easily travels around the globe and can develop drug-resistant strains if not properly treated. The End TB Now Act would catalyze research for an effective vaccine and new drugs to fight resistance. It would strengthen coordination with other governments and global organizations, and set bold goals for detection, treatment and prevention. For accountability, Congress would require performance evaluations of supported programs and annual reports specifying impact.

These bills make our foreign development funds more effective while saving and improving lives. Congress should pass both these bills as soon as possible when it resumes in 2024.

Anne Child

Oak Ridge

Bob Hughes, right, then nine, and his brother Dick, seven, at the tuberculosis sanitorium in Akron, Ohio in 1932. Bob turned 100 on Feb. 1, 2023. Dick died in 2012 at age 87.

This article originally appeared on Oakridger: Letter: Congress needs to take action on READ, End TB Now acts

View comments

Vaccine Boosts Innate Immunity In People With Dormant Immune Cells

image:

Graphical abstract of the BCG vaccine trained immunity study

Credit: Immunity

Humans are protected by two branches of the immune system. Innate immunity provides built-in defense against widespread characteristics of bacteria and viruses, while adaptive immunity memorizes individual pathogens that a person has already encountered. Vaccines teach the adaptive immune system about new pathogens without having to go through an actual infection. This has greatly contributed to human health, but requires a specific vaccine for each major pathogen.

Some vaccines not only teach the adaptive immune system about a specific pathogen, but also increase the overall vigilance of our body's innate immune cells. The BCG vaccine, which teaches our adaptive immune system to fight tuberculosis bacteria, has been shown to reduce infant mortality independent of its protection against tuberculosis. This observation can be explained by the concept of "trained immunity" – the idea that innate immune cells can switch between dormant and vigilant states, and are more effective at fighting infection when in their vigilant state.

Not every immune cell needs training

Inducing trained immunity by drugs or vaccines could confer protection in times of high infection risk, for example following a major surgery or during future pandemics before tailored vaccines become available. However, trained immunity is highly variable between individuals, and it is not well understood who may profit from inducing trained immunity.

To investigate this issue, a team led by Mihai Netea (Radboud University Medical Center) and Christoph Bock (CeMM & Medical University of Vienna) vaccinated 323 healthy volunteers with BCG and analyzed the effects on the immune system. They found that the induction of trained immunity was most effective in individuals with dormant innate immunity, which was reflected in a characteristic epigenetic cell state that predicted the vaccine response (Moorlag SJCFM, Folkman L, ter Horst R, Krausgruber T, et al. Immunity. 2024).

The team identified 213 individuals as trained immunity responders and 78 as non-responders, based on whether or not their production of inflammatory mediators had increased at day 90 after BCG vaccination – at a point when the acute response has subsided, but trained immunity is expected to persist. Trained immunity responders produced fewer mediators before vaccination and started with more dormant innate immune cells than non-responders. In other words, the non-responders already had the higher immune vigilance that the BCG vaccine induced in the responders.

Epigenetic regulation of immune balance

Both genetic and environmental factors contributed to this variability, but the most interesting differences were observed in the epigenetic states of the immune cells. Epigenetic cell states, implemented through changes in chromatin accessibility that make genes easier or harder to activate, reflect the regulatory plasticity of a cell and its ability to respond rapidly to changes in its environment, making them strong candidates for regulating trained immunity.

Indeed, in response to BCG vaccination, trained immunity responders gained open chromatin at genes involved in innate immunity, while non-responders carried such open chromatin independent of BCG vaccination, with no further increase following the vaccination. This finding explains how epigenetics allows immune cells to switch between different levels of immune vigilance, which contributes to the need to balance immune activity to provide protection against pathogens while avoiding unnecessary and harmful immune responses.

The study also clarifies a previously observed association between scar development at the site of BCG vaccination on the skin and lower child mortality. Previously, scar formation at the vaccine injection site was interpreted as a sign of a strong immune response to the vaccine. However, the team's analyses offer an alternative explanation: it seems that scar formation reflects strong immunity prior to vaccination, and these individuals may be better protected against infections independent of BCG vaccination.

Enhancing immune vigilance

These results not only provide new insights into immune biology and the role of epigenetics, but also guide the development of future therapeutics. "We can envision a new class of drugs that deliberately wake up a dormant immune system," Netea says. "Elderly people could receive a boost of their immune system prior to a planned hospital stay, and it may be possible to reactivate the suppressed immune system in patients with cancer. Several pharmaceutical companies are already pursuing ways to induce trained immunity without having to rely on the BCG vaccine."

The new study provides important guidance for such endeavors. First, a better understanding of the biological pathways underlying trained immunity may uncover novel therapeutic targets. Second, the study shows that such therapeutics are only likely to benefit individuals with dormant innate immunity, who can be identified through chromatin profiling or functional immune assays. Third, no overshooting immune responses were observed in individuals with high innate immunity prior to vaccination, which bodes well for the safety of future trained immunity inducing drugs.

Bock summarizes: "Our study highlights the close connection between epigenetic cell states and trained immunity, allowing the human body to switch between vigilant and dormant innate immunity. This process is variable across individuals and may be exploited with precision medicine."

+++

The study "Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity" was published in Immunity on January 9, 2024. DOI: 10.1016/j.Immuni.2023.12.005

Authors: Moorlag SJCFM*, Folkman L*, ter Horst R*, Krausgruber T*, Barreca D, Schuster LC, Fife V, Matzaraki V, Li W, Reichl S, Mourits VP, Koeken VACM, de Bree LCJ, Dijkstra H, Lemmers H, van Cranenbroek B, van Rijssen E, Koenen HJPM, Joosten I, Xu C-J, Li Y, Joosten LAB, van Crevel R, Netea MG#, Bock C# (* Contributed equally # Senior authors)

Funding: This study was supported by a Marie Skłodowska-Curie Actions Individual Fellowship (L.F.), an EMBO Postdoctoral Fellowship (R.T.H.), the European Research Council (M.G.N. And C.B.), the European Union's Horizon 2020 research and innovation program (M.G.N. And L.A.B.J.), the Netherlands Organization for Scientific Research (M.G.N.), and two Austrian Science Fund Special Research Area grants (C.B.).

Christoph Bock is a Principal Investigator at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and Professor of [Bio]Medical Informatics at the Medical University of Vienna. He is also the scientific coordinator of the Biomedical Sequencing Facility at CeMM, member of the Human Cell Atlas Organizing Committee, fellow of the European Lab for Learning and Intelligent Systems (ELLIS), and co-founder of a Vienna-based start-up company (Myllia Biotechnology). He has received major research awards, including an ERC Starting Grant (2016-2021), an ERC Consolidator Grant (2021-2026), the Otto Hahn Medal of the Max Planck Society (2009), the Overton Prize of the International Society for Computational Biology (2017), and the Erwin Schrödinger Prize of the Austrian Academy of Sciences (2022).

Mihai Netea heads the division of Experimental Medicine, Department of Internal Medicine, Radboud University Medical Center in Nijmegen. He is scientific founder of the biotech start-up companies Trained Therapeutix Discovery and Lemba, and of the biotech incubator Biotrip. He is mainly interested in understanding the memory traits of innate immunity (trained immunity) and has received major grants such as ERC Consolidator (2012-2017) and ERC Advanced (2019-2024). He is elected fellow of the Infectious Diseases Society of America, recipient of the van Loghem Award of the Netherlands Society of Immunology, and of the Spinoza Prize (2016). Since 2016 he is a member of the Netherlands Royal Academy of Sciences (KNAW).

The CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences is an international, independent and interdisciplinary research institution for molecular medicine under the scientific direction of Giulio Superti-Furga. CeMM is oriented towards medical needs and integrates basic research and clinical expertise to develop innovative diagnostic and therapeutic approaches for precision medicine. Research focuses on cancer, inflammation, metabolic and immune disorders, and rare diseases. The Institute's research building is located on the campus of the Medical University and the Vienna General Hospital.

www.Cemm.At

The Medical University of Vienna is one of the most traditional medical education and research facilities in Europe. With almost 8,000 students, it is currently the largest medical training center in the German-speaking countries. With 6,000 employees, 30 departments and two clinical institutes, 13 medical theory centers and numerous highly specialized laboratories, it is one of Europe's leading research establishments in the biomedical sector. MedUni Vienna also has a medical history museum, the Josephinum.

www.Meduniwien.Ac.At

The Radboud University Medical Center is one of seven academic medical centers in the Netherlands. With ~11,100 employees it provides patient care, teaching (BSc and MSc medical and biomedical sciences, and postgraduate courses) and research. The center's mission in scientific research is to advance human knowledge by conducting biomedical, translational and clinical research in order to improve wellbeing. Its key strength is medical life sciences and clinical practice, with an infrastructure comprising of state-of-the-art technology platforms and (translational) research facilities.

www.Radboudumc.Nl

For further information please contact:

Stefan Bernhardt

PR & Communications Manager

CeMM

Research Center for Molecular Medicine

of the Austrian Academy of Sciences

Lazarettgasse 14, AKH BT 25.3

1090 Vienna, Austria

Phone +43-1/40160-70 056

Mobile +43 660 3408133

sbernhardt@cemm.At

www.Cemm.At

Method of Research

Data/statistical analysis

Subject of Research

Cells

Article Title

Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity

Article Publication Date

9-Jan-2024

Search This Blog

Mumps