(Press-News.org)
Niigata, Japan - Tuberculosis is still one of the deadliest infectious diseases, causing over one million deaths each year worldwide. Additionally, about one-fourth of the world's population carries Mycobacterium tuberculosis (M. tuberculosis) without showing any symptoms, and most of these carriers do not develop the disease.
The current anti-tuberculosis vaccine, BCG, is administered worldwide. However, considering that more than 10 million new tuberculosis cases are reported each year, its effectiveness is deemed insufficient. As a result, the development of vaccines to replace BCG is underway. However, no new vaccine has yet surpassed BCG, which is a highly effective live vaccine. Actually BCG is very effective in preventing tuberculosis in children, creating a booster vaccine to strengthen immunity in adults is considered a promising and realistic option.
In developing tuberculosis vaccines, scientists have studied proteins from M. tuberculosis that trigger the protective immunity against tuberculosis. Especially IFN-gamma produced by T cells is known to be critical for protection against tuberculosis. Thus IFN-gamma responses are marker of vaccine candidate antigens and efficacy. However there's a paradoxical situation where proteins that induce higher IFN-gamma production in tuberculosis patients, who already have developed the disease, rather than in asymptomatic carriers who prevent its onset, are being viewed as potential vaccine candidates. Furthermore, many of vaccine studies ignore the native three-dimensional structure of the proteins and the modification they undergo after being translated in M. tuberculosis.
On the productivity side, vaccine candidate molecules are being made in basic model organisms like Escherichia coli. However, certain molecules undergo specific changes after translation that are unique to the pathogen, such as M. tuberculosis.
It's been noted that these modifications might be crucial for mounting effective defenses against actual pathogen attacks.
Mycobacterial DNA-binding protein 1 (MDP1) is a major protein of both BCG and M. tuberculosis (Shaban et al., Sci Rep., 2024) with extensive post-translational modifications (Yoshida et al., BBRC., 2023). Recent studies show that IFN-gamma responses to MDP1 are higher in individuals who suppress tuberculosis progression compared to tuberculosis patients, making MDP1 a new vaccine candidate (Yasuda et al., Front Immunol., 2024). To evaluate MDP1 for a tuberculosis booster vaccine, Ozeki et al. produced recombinant MDP1 and tested its ability to induce IFN-gamma using blood from BCG-vaccinated adults.
Ozeki et al., expressed MDP1 in two different hosts: M. smegmatis, a non-pathogenic, fast-growing mycobacteria, and E. coli. Importantly, the MDP1 expressed in M. smegmatis (mMDP1) showed significant post-translational modifications, closely resembling the native MDP1 found in M. tuberculosis, while the one expressed in E. coli (eMDP1) did not.
When they cultured both variants of MDP1 with peripheral blood from adults vaccinated with BCG, they observed that mMDP1 triggered notably higher levels of IFN-gamma production compared to eMDP1. This implies that the immune system of BCG-vaccinated adults can recognize MDP1 with post-translational modifications.
Importantly, mMDP1 demonstrated a superior capacity for IFN-gamma production compared to other vaccine candidate antigens, such as Antigen 85 complex, which is currently in development. When utilizing protein antigens as vaccines, adjuvants are typically employed to prevent degradation or enhance immunogenicity. We previously reported that MDP1, due to its binding affinity to bacterial DNA, has protected mice from M. tuberculosis infection when co-administered. In this study we also demonstrated that the combination of mMDP1 and G9.1, a novel type of CpG-DNA, elicits a significant level of IFN-gamma from peripheral blood of BCG-vaccinated adults.
The results of this study suggest that combining mMDP1, which displays post-translational modifications, with G9.1 can reinvigorate the waning effect of BCG, indicating its potential as a booster vaccine.
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USC recently hosted its first Music, Health, and Policy workshop as part of Los Angeles County Arts and Health Week, filling Joyce J. Cammilleri Hall on the University Park Campus.
Event organizer Assal Habibi, an associate professor at the Brain and Creativity Institute at the USC Dornsife College of Letters, Arts and Sciences who explores the intersection between music and the human brain, brought together a wide range of experts on the importance of art and its effect on human development and well-being.
“The workshop aims to bring people together ...
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A multi-institutional study led by University of Illinois and Agroecosystem Sustainability Center (ASC) scientists concluded that, although soil moisture varies significantly both within a single field and from field to field due to varying soil properties and different management practices, soil moisture distribution relative to the field average remains consistent across time within each field.
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As space travel becomes more common, it is important to consider the impacts of space flight and altered gravity on the human body. Led by Dr. Ana Diaz Artiles, researchers at Texas A&M University are studying some of those impacts, specifically effects on the eye.
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(Santa Barbara, Calif.) — Haewon Jeong, an assistant professor in UC Santa Barbara’s Electrical and Computer Engineering (ECE) Department, experienced a pivotal moment in her academic career when she was a postdoctoral fellow at Harvard University. She was investigating how machine learning (ML) models can discriminate against students in education-related applications. Discrimination, or bias, occurs when a model used to train algorithms makes incorrect predictions that systematically disadvantage a group of people. Bias in ML models can lead to inaccurate or unfair predictions, which can have serious consequences in fields such as healthcare, finance and criminal justice. ...
University of Toronto engineering researchers have designed a new way to recycle steel that has the potential to decarbonize a range of manufacturing industries and usher in a circular steel economy.
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June 18, 2024
Non-native Plants and Animals Expanding Ranges 100 Times Faster than Native Species, Finds New Research Led by UMass Amherst
Native species cannot move fast enough on their own to avoid climate-driven chaos
AMHERST, Mass. – An international team of scientists has recently found that non-native species are expanding their ranges many orders of magnitude faster than native ones, in large part due to inadvertent human help. Even seemingly sedentary non-native plants are moving at three times the speed ...