Review
Immunology
Shivani Singh, Noemi Alejandra Saavedra-Avila, Sangeeta Tiwari, Steven A. Porcelli
Summary: BCG has been used as a tuberculosis vaccine since 1921 and is currently the only approved vaccine for this infection. Recent research has shown that BCG not only protects against disease progression, but also against initial infection, highlighting the importance of understanding the immune mechanisms involved. This review explores the components of immunity enhanced by BCG vaccination, and the efforts to improve its efficacy through recombinant strains and non-traditional routes. The ability of BCG to confer trained immunity in a non-specific manner is also discussed.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Paulo R. Z. Antas, Andreon S. M. da Silva, Lawrence H. P. Albuquerque, Matheus R. Almeida, Evelyn N. G. S. Pereira, Luiz R. R. Castello-Branco, Carlos G. G. de Ponte
Summary: This study investigates the protective role of BCG in inducing surface biomarkers and analyzes the expression levels of TLR4, B7-1, Dectin-1, EP2, and TIM-3 in monocytes. The results uncover the regulatory effect of BCG on these biomarkers and emphasize the importance of understanding human innate immune responses for vaccine development and infectious disease treatment.
Article
Immunology
Rania Bouzeyen, Saurabh Chugh, Tannu Priya Gosain, Mohamed-Ridha Barbouche, Meriam Haoues, Kanury V. S. Rao, Makram Essafi, Ramandeep Singh
Summary: This study demonstrates that enhancing the protective efficacy of M. bovis BCG in mice and guinea pig infection models by inhibiting Akt inhibitor MK-2206 promotes FOXO3 activation and BCG-induced immune responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Mitchell Foster, Philip C. Hill, Todia Pediatama Setiabudiawan, Valerie A. C. M. Koeken, Bachti Alisjahbana, Reinout van Crevel
Summary: This review examines the protective effect of BCG vaccine against Mtb infection, discusses limitations and variations, and explores potential mechanisms for BCG efficacy against Mtb infection, including the role of trained immunity.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Immunology
Julia Bitencourt, Marco Polo Peralta-Alvarez, Morven Wilkie, Ashley Jacobs, Daniel Wright, Salem Salman Almujri, Shuailin Li, Stephanie A. Harris, Steven G. Smith, Sean C. Elias, Andrew D. White, Iman Satti, Sally S. Sharpe, Matthew K. O'Shea, Helen McShane, Rachel Tanner
Summary: Tuberculosis is a major health problem worldwide, and the currently-licensed BCG vaccine is not effective enough. Research has shown that the BCG vaccine can induce specific antibodies, which play a crucial role in cellular defense. These findings suggest that the humoral immune response should be further investigated in TB vaccine development.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Nonna I. Nadolinskaia, Maria S. Kotliarova, Anna V. Goncharenko
Summary: Tuberculosis is a major infectious disease with high mortality rates in certain regions, and the existing BCG vaccine is ineffective for long-term protection. The exact immune factors crucial for preventing Mycobacterium tuberculosis infection and progression of the disease are still unknown after decades of research. Developing a new vaccine to replace BCG and provide better protection is a challenging task due to the intracellular lifestyle of the pathogen and its manipulation of host immunity. This review discusses promising strategies and possibilities for creating a new vaccine, including supplementing mycobacterial strains with immunodominant antigens and genetic engineering to alter the bacterium-host cell interaction.
Review
Biochemistry & Molecular Biology
Layaly Shkair, Ekaterina E. Garanina, Robert J. Stott, Toshana L. Foster, Albert A. Rizvanov, Svetlana F. Khaiboullina
Summary: The prevention and control of infectious diseases is crucial, with vaccination being an effective approach. Microvesicles are suggested as potential vehicles for antigen delivery, carrying various immunogenic molecules directly to target cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Azra Blazevic, Rachel L. Edwards, Mei Xia, Christopher S. Eickhoff, Fahreta Hamzabegovic, Krystal A. Meza, Huan Ning, Janice Tennant, Karla J. Mosby, James C. Ritchie, Tigisty Girmay, Lilin Lai, Michele Mccullough, Allison Beck, Colleen Kelley, Srilatha Edupuganti, Sarah Kabbani, Wendy Buchanan, Mamodikoe K. Makhene, Delia Voronca, Sami Cherikh, Johannes B. Goll, Nadine G. Rouphael, Mark J. Mulligan, Daniel F. Hoft
Summary: This study demonstrates that the BCG human challenge model is a feasible approach for assessing in vivo tuberculosis immunity and could facilitate the vaccine development process. The results provide valuable insights into potential biomarkers of mycobacterial immunity and transcriptomic analyses that may aid in understanding the immune component underlying the higher rate of TB disease incidence in males.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Medicine, Research & Experimental
Rocky Lai, Diana N. Gong, Travis Williams, Abiola F. Ogunsola, Kelly Cavallo, Cecilia S. Lindestam Arlehamn, Sarah Acolatse, Gillian L. Beamer, Martin T. Ferris, Christopher M. Sassetti, Douglas A. Lauffenburger, Samuel M. Behar
Summary: In this study, we investigated the influence of host genetics on Bacillus Calmette Guerin-induced immunity against Mycobacterium tuberculosis in 24 collaborative cross (CC) mouse strains. We found that host genetics plays a major role in BCG-induced immunity against M. tuberculosis infection, which poses a barrier to vaccine-mediated protection. Furthermore, BCG efficacy is independent of inherent susceptibility to tuberculosis, and the composition of T cells in the lung after infection is mainly determined by host genetics rather than BCG vaccination.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Review
Virology
Fengling Feng, Ziyu Wen, Jiaoshan Chen, Yue Yuan, Congcong Wang, Caijun Sun
Summary: Mucosal vaccines are a promising strategy for superior protection against pathogens, but face challenges such as poor adhesion and uptake. Efforts have been made to overcome these issues, including novel administration routes and the development of mucosa-targeting vectors and adjuvants.
Review
Infectious Diseases
Gopala Koneru, Gaber El-Saber Batiha, Abdelazeem M. Algammal, Mahmoud Mabrok, Sara Magdy, Shrouk Sayed, Mai E. AbuElmagd, Reham Elnemr, Mahmoud M. Saad, Noura H. Abd Ellah, Amal Hosni, Khalid Muhammad, Helal F. Hetta
Summary: Studies suggest that BCG may induce trained immunity to provide some protection against SARS-CoV-2. Repurposing the well-characterized BCG during the COVID-19 pandemic could offer some degree of protection to the population.
INFECTION AND DRUG RESISTANCE
(2021)
Review
Microbiology
Stefan H. E. Kaufmann
Summary: The year 2020 was marked by the COVID-19 pandemic, but also brought hope with the development of vaccines. While the BCG vaccine has saved millions of lives, current vaccines are still insufficient. Recent advancements in novel vaccine development show promise, but the effectiveness of controlling tuberculosis remains uncertain.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Alice Italia, Mohammed Monsoor Shaik, Francesco Peri
Summary: This review presents and discusses emerging pharmacological strategies that target major virulence factors of antibiotic-resistant Mycobacterium tuberculosis (Mtb). It is divided into three parts focusing on the cell wall, lipoarabinomannan, and secretory proteins, which play important roles in Mtb pathogenicity. The article provides a comprehensive overview of drugs and drug candidates that target cell walls, envelopes, and secretory systems, and also highlights the molecular understanding of Mtb pathogenesis and potential future directions in therapeutic strategies for combating antibiotic-resistant Mtb infection.
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
Infectious Diseases
Fathiah Zakham, Tarja Sironen, Olli Vapalahti, Ravi Kant
Summary: This study aimed to conduct a comparative genome analysis of human adapted Mycobacterium tuberculosis complex species, including BCG vaccine strains, to identify and pinpoint conserved genes related to virulence across all species. The core genome consists of 1166 conserved genes among these species, representing a small portion of the 7036 genes in the pan-genome, suggesting potential for vaccine candidate development.
Article
Biotechnology & Applied Microbiology
Francesca Boldrin, Giulia Degiacomi, Agnese Serafini, Gaelle S. Kolly, Marcello Ventura, Claudia Sala, Roberta Provvedi, Giorgio Palu, Stewart T. Cole, Riccardo Manganelli
MICROBIAL BIOTECHNOLOGY
(2018)
Article
Cell Biology
Flavio De Maio, Basem Battah, Valentina Palmieri, Linda Petrone, Francesco Corrente, Alessandro Salustri, Ivana Palucci, Silvia Bellesi, Massimiliano Papi, Salvatore Rubino, Michela Sali, Delia Goletti, Maurizio Sanguinetti, Riccardo Manganelli, Marco De Spirito, Giovanni Delogu
CELLULAR MICROBIOLOGY
(2018)
Article
Multidisciplinary Sciences
Francesca Boldrin, Saber Anoosheh, Agnese Serafini, Laura Cioetto Mazzabo, Giorgio Palu, Roberta Provvedi, Riccardo Manganelli
SCIENTIFIC REPORTS
(2019)
Article
Immunology
Rogelio Hernandez-Pando, Sung Jae Shin, Simon Clark, Stefano Casonato, Martin Becerril-Zambrano, Hongmin Kim, Francesca Boldrin, Dulce Mata-Espinoza, Roberta Provvedi, Ainhoa Arbues, Brenda Marquina-Castillo, Laura Cioetto Mazzabo, Jorge Barrios-Payan, Carlos Martin, Sang-Nae Cho, Ann Williams, Riccardo Manganelli
INFECTION AND IMMUNITY
(2020)
Review
Microbiology
Francesca Boldrin, Roberta Provvedi, Laura Cioetto Mazzabo, Greta Segafreddo, Riccardo Manganelli
FRONTIERS IN MICROBIOLOGY
(2020)
Review
Cell Biology
Alessandro Sinigaglia, Elektra Peta, Silvia Riccetti, Seshasailam Venkateswaran, Riccardo Manganelli, Luisa Barzon
Article
Cell Biology
Haoting Hsu, Sarah Boudova, Godfrey Mvula, Titus H. Divala, David Rach, Randy G. Mungwira, Francesca Boldrin, Giulia Degiacomi, Riccardo Manganelli, Miriam K. Laufer, Cristiana Cairo
Summary: Infant Vδ2 lymphocytes exhibit intermediate or adult-like expression of markers associated with differentiation or function, intermediate proliferative responses, and adult-like cytotoxic potential. The enhancement of Vδ2 cell cytotoxic potential coincided with decreasing PD-1 and increasing NKG2A expression, suggesting a shift in mechanisms regulating Vδ2T cell function during infancy.
CELLULAR IMMUNOLOGY
(2021)
Article
Microbiology
Francesca Boldrin, Itxaso Anso, Sogol Alebouyeh, Iker A. Sevilla, Marivi Geijo, Joseba M. Garrido, Alberto Marina, Laura Cioetto Mazzabo, Greta Segafreddo, Marcelo E. Guerin, Riccardo Manganelli, Rafael Prados-Rosales
Summary: The research highlights the vital role of PatA, an acyltransferase involved in the PIM biosynthetic pathway, for the survival and virulence of Mycobacterium tuberculosis. Silencing the patA gene leads to bactericidal effects in vitro and in vivo, underscoring the potential of PatA as a novel drug target against this major human pathogen.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Microbiology
Francesca Boldrin, Laura Cioetto Mazzabo, Marie-Antoinette Laneelle, Laura Rindi, Greta Segafreddo, Anne Lemassu, Gilles Etienne, Marta Conflitti, Mamadou Daffe, Alfredo Garzino Demo, Riccardo Manganelli, Hedia Marrakchi, Roberta Provvedi
Summary: In this study, we characterized a protein encoded by the Mtb genome, Rv1619, and found that it is a potential member of the aaPG synthase family. Unlike previous studies, we predicted that the MprF-like domain of Rv1619 is located in the extracytoplasmic region.
Review
Immunology
Paolo Miotto, Rita Sorrentino, Stefano De Giorgi, Roberta Provvedi, Daniela Maria Cirillo, Riccardo Manganelli
Summary: Bacterial drug resistance poses a serious threat to human health, with tuberculosis being a high-risk infection due to limited drugs available against Mycobacterium tuberculosis. Drug resistance in bacteria is often caused by point mutations in drug targets, but changes in transcriptional regulation post-drug exposure also play a significant role and should be further explored for potential new drug targets and intervention strategies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Francesca Boldrin, Laura Cioetto Mazzabo, Saber Anoosheh, Giorgio Palu, Luc Gaudreau, Riccardo Manganelli, Roberta Provvedi
SCIENTIFIC REPORTS
(2019)
Review
Immunology
Flavio De Maio, Rita Berisio, Riccardo Manganelli, Giovanni Delogu