Article
Immunology
Huanhuan Ning, Jian Kang, Yanzhi Lu, Xuan Liang, Jie Zhou, Rui Ren, Shan Zhou, Yong Zhao, Yanling Xie, Lu Bai, Linna Zhang, Yali Kang, Xiaojing Gao, Mingze Xu, Yanling Ma, Fanglin Zhang, Yinlan Bai
Summary: In this study, researchers constructed a recombinant BCG vaccine (rBCG-DisA) with di-adenylate cyclase (DisA) and found that it induced enhanced immune responses in mice, leading to trained immunity and adaptive immunity. Additionally, rBCG-DisA showed promising potential in protecting against M. tuberculosis infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jiang Pi, Zhiyi Zhang, Enzhuo Yang, Lingming Chen, Lingchan Zeng, Yiwei Chen, Richard Wang, Dan Huang, Shuhao Fan, Wensen Lin, Hongbo Shen, Jun-Fa Xu, Gucheng Zeng, Ling Shen
Summary: Engineering Mycobacterium tuberculosis into nanoscale particles improves the safety and efficacy of the TB vaccine, providing better protection against TB infection.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Immunology
Magdalena Druszczynska, Michal Seweryn, Sebastian Wawrocki, Anna Pankowska, Magdalena Godkowicz, Magdalena Kowalewska-Pietrzak
Summary: The study evaluated the utility of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in identifying latent tuberculosis infection (LTBI) in BCG-vaccinated Polish children and adolescents exposed to contagious TB. The study also investigated if quantitative assessment of IGRA results could predict active TB disease. The results showed that both TST and IGRA can be used as screening tests for BCG-vaccinated children and adolescents exposed to contagious TB.
Review
Biochemistry & Molecular Biology
Marek Fol, Piotr Kozinski, Jakub Kulesza, Piotr Bialecki, Magdalena Druszczynska
Summary: Recent studies suggest that chronic inflammation related to mycobacteria may be a possible mechanism of cancer pathogenesis. Different types of mycobacterial infections, such as Mycobacterium tuberculosis, non-tuberculous Mycobacterium avium complex, and Mycobacterium ulcerans, have been associated with increased risks of lung cancer and skin carcinogenesis. The relationship between chronic mycobacterial infections and tumor development is thought to involve various host effector mechanisms at different stages of oncogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Kuan-Chun Huang, Dinesh Chanda, Shannon McGrath, Vaishali Dixit, Chi Zhang, Jiayi Wu, Karen Tendyke, Huilan Yao, Renee Hukkanen, Noel Taylor, David Verbel, Dae-Shik Kim, Atsushi Endo, Thomas A. Noland, Yu Chen, Mark Matijevic, John Wang, Janna Hutz, Nadeem Sarwar, Francis G. Fang, Xingfeng Bao
Summary: This study demonstrates that the use of macrocyle-bridged STING agonist E7766 can induce antitumor effects in vitro and in vivo via intravesical instillation in NMIBC tumor models resistant to BCG and anti-PD-1 agents. Activation of the STING pathway in the bladder results in immune cell infiltration and antigen presentation, leading to antitumor activity and immunity. This research provides a rationale for subsequent clinical studies in NMIBC patients.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Irene Perez, Elena Campos-Pardos, Caridad Diaz, Santiago Uranga, Fadel Sayes, Francisca Vicente, Nacho Aguilo, Roland Brosch, Carlos Martin, Jesus Gonzalo-Asensio
Summary: Cyclic (di)nucleotides act as universal second messengers and are produced by several pathogens. In this study, the researchers investigated the role of c-di-AMP in Mycobacterium tuberculosis and its contribution to tuberculosis vaccines. They found that c-di-AMP synthesis is regulated by the M. tuberculosis PhoPR virulence system and that MTBVAC, a live attenuated tuberculosis vaccine, produces higher levels of c-di-AMP compared to wild-type M. tuberculosis or the current BCG vaccine. They also discovered that c-di-AMP levels are dependent on the growth phase and medium during in vitro cultivation of M. tuberculosis. Furthermore, they demonstrated that increasing c-di-AMP levels correlated with a safer profile of tuberculosis vaccines in an immunodeficient mouse model.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Review
Medicine, Research & Experimental
Benjamin N. Koleske, William R. Jacobs, William R. Bishai
Summary: The complete genome sequence of Mycobacterium tuberculosis, achieved in 1998, has provided invaluable insights and tools for understanding tuberculosis. Whole-genome sequencing has improved our ability to predict antibacterial susceptibility and track epidemics. It also helps in studying the effectiveness of TB vaccines and identifying targets for new treatments.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Manuja Gunasena, Rajni Kant Shukla, Naiquan Yao, Oscar Rosas Mejia, Michael D. Powell, Kenneth J. Oestreich, Michel de Jesus Aceves-Sanchez, Mario Alberto Flores-Valdez, Namal P. M. Liyanage, Richard T. Robinson
Summary: The BCG Delta BCG1419c vaccine candidate exhibits longer survival time in intravenously infected BALB/c mice and provides better protection by reducing lung pathology in chronic stages of infection. The use of BCG Delta BCG1419c also results in lower levels of proinflammatory cytokines and shows differences in early immunological events compared to BCG-immunized mice, indicating its potential as an alternative TB vaccine candidate.
SCIENTIFIC REPORTS
(2022)
Article
Veterinary Sciences
Saraswathi Subramanian, Sreenidhi Srinivasan, Kathiravan Ramaiyan Selvaraju, Priyadharshini Michael Vinoli, Suganya Selladurai, Boominathan Ramasamy, Karthik Kumaragurubaran, Douwe Bakker, Martin Vordermeier, Vivek Kapur, Dhinakar Raj Gopal
Summary: The BCG vaccine provides partial protection against bovine tuberculosis in cattle. A peptide-based defined antigen skin test (DST) has been developed to differentiate between BCG-vaccinated and bTB-infected animals. This study demonstrates that DST retains its diagnostic specificity even after revaccination with BCG.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Multidisciplinary Sciences
Emilie Jalbert, Cuining Liu, Vidya Mave, Nancy Lang, Anju Kagal, Chhaya Valvi, Mandar Paradkar, Nikhil Gupte, Rahul Lokhande, Renu Bharadwaj, Vandana Kulkarni, Amita Gupta, Adriana Weinberg
Summary: There is a need for more effective vaccines against tuberculosis (TB) than the currently licensed BCG vaccine. This study aimed to identify new vaccine benchmarks by examining immune responses in individuals able to eradicate the infection (TB-resisters) and individuals with latent infection (LTBI-participants). Results showed that TB-resisters had higher frequencies of certain T cells and higher proportions of polyfunctional T cells expressing specific markers, while LTBI-participants had higher expression of activation markers and cytokines. The findings suggest that specific T cell responses may be desirable for new TB vaccines.
Article
Immunology
Karin Dijkman, Thomas Lindenstrom, Ida Rosenkrands, Rikke Soe, Joshua S. S. Woodworth, Cecilia S. Lindestam S. Arlehamn, Rasmus Mortensen
Summary: The licensed TB vaccine, BCG, is inadequate in protecting adolescents and adults from pulmonary TB, leading to millions of deaths each year. Subunit vaccines have shown potential against TB, but their multiple administrations pose logistical challenges. Co-administration of BCG with a single dose of the expression-optimized H107e/CAF((R))01 vaccine improved protection and triggered BCG-specific immune responses. This supports the strategy of combining BCG with subunit vaccines for an improved TB vaccine with fewer vaccination visits.
Article
Biology
Qingmei Jia, Sasa Maslesa-Galic, Susana Nava, Marcus A. Horwitz
Summary: This study developed new tuberculosis vaccines based on attenuated recombinant Listeria monocytogenes and evaluated them in mouse and guinea pig models. The vaccines showed good safety, immunogenicity, and efficacy, indicating their potential as new tuberculosis vaccines.
COMMUNICATIONS BIOLOGY
(2022)
Article
Immunology
Wei Huang, Nan-Chang Chiu, Hsin Chi, Fu-Yuan Huang, Ching-Ying Huang
Summary: A study on BCG vaccine adverse reactions found that osteitis/osteomyelitis occurred less frequently when vaccination was done after 5 months of age, but injection site reactions and lymphadenitis were more common, with shorter onset durations of mild adverse reactions observed in older vaccinees above 5 months of age.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Medicine, Research & Experimental
Mathieu Rouanne, Julien Adam, Camelia Radulescu, Diane Letourneur, Delphine Bredel, Severine Mouraud, Anne-Gaelle Goubet, Marion Leduc, Noah Chen, Tuan Zea Tan, Nicolas Signolle, Amelie Bigorgne, Michael Dussiot, Lambros Tselikas, Sandrine Susini, Francois-Xavier Danlos, Anna K. Schneider, Roman Chabanon, Sophie Vacher, Ivan Bieche, Thierry Lebret, Yves Allory, Jean-Charles Soria, Nicholas Arpaia, Guido Kroefinet, Oliver Kepp, Jean Paul Thiery, Laurence Zitvogel, Aurelien Marabelle
Summary: In patients with high-risk, nonmuscle-invasive bladder cancer (NMIBC), two distinct patterns of immune subversion upon BCG relapse have been identified, which can predict the prognosis of the patients.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biotechnology & Applied Microbiology
Saba Savul, Susan Duthie
Summary: This study reviewed the BCG vaccination records from 2019 to 2021 in Grampian, Scotland and found a high uptake rate, surpassing the key performance indicator target in Scotland and showing improvement compared to earlier rates. Strengthening electronic systems and raising awareness can further enhance BCG vaccination uptake.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
Article
Cell Biology
Mohd Shariq, Neha Quadir, Javaid Ahmad Sheikh, Alok Kumar Singh, William R. Bishai, Nasreen Z. Ehtesham, Seyed E. Hasnain
Summary: The host utilizes ubiquitin pathway to combat intracellular pathogens, while pathogens like Mycobacterium tuberculosis exploit this pathway to dampen host innate immune response.
Article
Radiology, Nuclear Medicine & Medical Imaging
Camilo A. Ruiz-Bedoya, Filipa Mota, Alvaro A. Ordonez, Catherine A. Foss, Alok K. Singh, Monali Praharaj, Farina J. Mahmud, Ali Ghayoor, Kelly Flavahan, Patricia De Jesus, Melissa Bahr, Santosh Dhakal, Ruifeng Zhou, Clarisse Solis, Kathleen R. Mulka, William R. Bishai, Andrew Pekosz, Joseph L. Mankowski, Jason Villano, Sabra L. Klein, Sanjay K. Jain
Summary: This study utilized pulmonary PET/CT with I-124-iodo-DPA-713 to evaluate the local immune response in a hamster model of SARS-CoV-2 infection, revealing worse pulmonary disease in male hamsters compared to females, with higher I-124-iodo-DPA-713 PET activity in the infected areas.
MOLECULAR IMAGING AND BIOLOGY
(2022)
Article
Education, Scientific Disciplines
Alok Kumar Singh, Sivaprakash Ramalingam, Desirazu N. Rao, Srinivasan Chandrasegaran
Summary: Programmable nucleases like ZFNs, TALENs, and CRISPR-Cas9 provide scientists with the unprecedented ability to modify cells and organisms at will, impacting various fields of life sciences. These technologies have expanded the possibilities of gene editing, with each type of nuclease offering unique advantages and applications in different research areas. The widespread adoption of CRISPR-Cas9 in particular reflects its simplicity and efficiency in genome editing, leading to its recognition with the 2020 Nobel Prize for Chemistry. However, concerns remain about off-target effects and ethical implications when applying these technologies to human therapeutics.
RESONANCE-JOURNAL OF SCIENCE EDUCATION
(2021)
Article
Oncology
Kara A. Lombardo, Aleksandar Obradovic, Alok Kumar Singh, James L. Liu, Gregory Joice, Max Kates, William Bishai, David McConkey, Alcides Chaux, Marie-Lisa Eich, M. Katayoon Rezaei, George J. Netto, Charles G. Drake, Phuoc Tran, Andres Matoso, Trinity J. Bivalacqua
Summary: In a murine model, BCG instillations elevated STING pathway activation and immune response, leading to tumor eradication, while radiotherapy induced immunosuppressive effects. In human non-muscle-invasive bladder cancer, STING protein expression was elevated in BCG responders and further increased after therapy. Overall, the study suggests that BCG has more beneficial effects on the bladder cancer immune microenvironment compared to radiation therapy.
JOURNAL OF PATHOLOGY
(2022)
Article
Immunology
Alok K. Singh, Geetha Srikrishna, Trinity J. Bivalacqua, William R. Bishai
Summary: The Bacillus Calmette-Guerin (BCG) vaccine, a live attenuated strain of Mycobacterium bovis, is widely used in global vaccination programs, but its efficacy against pulmonary TB in adults remains disputed. Modified BCG or alternative administration routes show promise in providing improved protection, while intravesical BCG is the primary therapy for non-muscle invasive bladder cancer (NMBIC). There is a critical need for improved intravesical therapies for NMBIC, with genetically modified BCG candidates showing potential as anti-tumor adjuvant therapy.
Article
Microbiology
Ruchi Jain Dey, Bappaditya Dey, Melanie Harriff, Elizabeth T. Canfield, David M. Lewinsohn, William R. Bishai
Summary: Mucosa-associated invariant T (MAIT) cells play a critical role in protecting the host against Mycobacterium tuberculosis infection. Overexpression of key genes in the riboflavin-biosynthetic pathway enhances MAIT cell activation and attenuates M. tuberculosis virulence. Increased MAIT cell abundance also results in better control of M. tuberculosis infection. Endogenously adjuvanted BCG vaccine with MR1 ligands can augment MAIT cell activation. These findings provide important insights into the role of the riboflavin-biosynthetic pathway, MAIT cell activation, M. tuberculosis virulence, and host immunity against TB.
Article
Multidisciplinary Sciences
Alok Kumar Singh, Monali Praharaj, Kara A. Lombardo, Takahiro Yoshida, Andres Matoso, Alex S. Baras, Liang Zhao, Geetha Srikrishna, Joy Huang, Pankaj Prasad, Jonathan D. Powell, Max Kates, David McConkey, Drew M. Pardoll, William R. Bishai, Trinity J. Bivalacqua
Summary: This study re-engineered the BCG vaccine to express high levels of the PAMP molecule c-di-AMP, leading to augmented immune responses, enhanced induction of trained immunity, and improved antitumor efficacy in pre-clinical models of bladder cancer.
NATURE COMMUNICATIONS
(2022)
Review
Multidisciplinary Sciences
Shifa Bushra Kotwal, Nidhi Orekondey, Gargi Prasad Saradadevi, Neha Priyadarshini, Navinchandra V. Puppala, Mahak Bhushan, Snehasri Motamarry, Rahul Kumar, Gireesha Mohannath, Ruchi Jain Dey
Summary: This review discusses the recent advances and potential novel molecular tools for viral diagnostics and therapeutics which have significant implications in future pandemic management. It highlights non-PCR-based methods for rapid and cost-effective detection of viral nucleic acids, along with advancements in miniaturized Lab-on-Chip devices for viral diagnosis and disease management. The review also explores underutilized antiviral strategies and plant-based platforms for large-scale production and oral delivery of antiviral agents/vaccines. Furthermore, it proposes repurposing existing vaccines, particularly the BCG-based vaccine engineering, for newer applications.
Article
Medicine, Research & Experimental
C. Korin Bullen, Alok K. Singh, Stefanie Krug, Shichun Lun, Preeti Thakur, Geetha Srikrishna, William R. Bishai
Summary: The host's cytosolic sensing of Mycobacterium tuberculosis (M. tuberculosis) RNA by the RIG-I-like receptor (RLR) family, specifically MDA5, plays a role in M. tuberculosis pathogenesis. Loss of MDA5 leads to a host protective effect, enhancing immune containment of M. tuberculosis both in vitro and in vivo, by inhibiting proinflammatory cytokine production, contributing to IL-1 beta production and inflammasome activation, and increasing autophagy.
Article
Multidisciplinary Sciences
Alok K. Singh, Rulin Wang, Kara A. Lombardo, Monali Praharaj, C. Korin Bullen, Peter Um, Manish Gupta, Geetha Srikrishna, Stephanie Davis, Oliver Komm, Peter B. Illei, Alvaro A. Ordonez, Melissa Bahr, Joy Huang, Anuj Gupta, Kevin J. Psoter, Patrick S. Creisher, Maggie Li, Andrew Pekosz, Sabra L. Klein, Sanjay K. Jain, Trinity J. Bivalacqua, Srinivasan Yegnasubramanian, William R. Bishai
Summary: BCG vaccine provides heterologous immune protection against SCV2 by promoting early lung antibody production and immunomodulating transcriptional patterns, resulting in reduced viral load and inflammation.
Review
Medicine, Research & Experimental
Alok K. Singh, Mihai G. Netea, William R. Bishai
Summary: BCG, first administered as a tuberculosis vaccine in 1921, has a long history of use for TB prevention and later for bladder cancer immunotherapy. It is estimated to be the most widely used vaccine in human history, with millions of doses procured annually. Apart from its traditional roles, BCG has been studied for nontraditional purposes, including prevention of viral infections, cancer immunotherapy, and immunologic diseases like multiple sclerosis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
