Journal of internal medicine
-
The most commonly used vaccine worldwide, bacillus Calmette-Guerin (BCG), appears to have the ability to restore blood sugar control in humans with early-onset but long-duration type 1 diabetes when a repeat vaccination strategy is used. This is a process that may be driven by a metabolic switch from overactive oxidative phosphorylation to accelerated aerobic glycolysis and a reset of the immune system. BCG is a live, attenuated strain of Mycobacteria bovis, a cousin of M. tuberculosis. ⋯ In recent times, humans have had fewer exposures to these and other microorganisms that historically helped shape the immune response. By 're-introducing' an attenuated form of Mycobacteria via BCG vaccination, humans might benefit from an immunological perspective, a concept supported by a growing body of data in autoimmunity and robust data on the nonspecific immune effects of BCG related to protection from diverse infections and early mortality. New findings of immune and metabolic defects in type 1 diabetes that can be corrected with repeat BCG vaccination suggest that this therapeutic strategy may be applicable in other diseases with inadequate aerobic glycolysis, including Parkinson's disease, dementia, depression and other disorders affecting the nervous system.
-
The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. ⋯ In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.
-
Tuberculosis remains a major source of morbidity and mortality worldwide, with 10 million cases and 1.5 million deaths in 2018. Achieving 'End TB' prevention and care goals by 2035 will likely require a new tuberculosis vaccine. The tuberculosis vaccine development pipeline has seen encouraging progress; however, questions around their population impact and implementation remain. ⋯ For BCG revaccination, the priority is completing the ongoing confirmation of efficacy trial. Critical modelling gaps remain on the full value proposition of vaccines, comparisons with other interventions and more realistic implementation strategies. Using carefully designed trials and modelling, we must prepare for success, to ensure that new vaccines will be promptly received by those most in need.
-
In recent years, the century-old Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been re-evaluated for its capacity to stem the global tide of TB. There is increasing evidence that the efficacy of BCG can be improved by the modified administration methods and schedules. Here, we first discuss recent approaches of vaccine administration, revaccination or boosting that have been used to try to improve the efficacy of BCG against TB. ⋯ These studies all highlight that there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity, which has been surprisingly understudied. We argue that several critical gaps in knowledge exist and must be addressed by future research to rationally improve the efficacy of BCG, including comprehensive, proteome-wide understanding of the epitopes derived from BCG recognized by BCG-vaccinated individuals, the phenotype of responding antigen-specific T cells and how previous exposure to environmental mycobacteria affect these parameters and thus influence vaccine efficacy. The development of modern techniques allows us to answer some of these questions to better understand how BCG works in terms of both protection against TB and the immune response that it triggers.
-
Senolytics are a class of drugs that selectively clear senescent cells (SC). The first senolytic drugs Dasatinib, Quercetin, Fisetin and Navitoclax were discovered using a hypothesis-driven approach. SC accumulate with ageing and at causal sites of multiple chronic disorders, including diseases accounting for the bulk of morbidity, mortality and health expenditures. ⋯ Early pilot trials of senolytics suggest they decrease senescent cells, reduce inflammation and alleviate frailty in humans. Clinical trials for diabetes, idiopathic pulmonary fibrosis, Alzheimer's disease, COVID-19, osteoarthritis, osteoporosis, eye diseases and bone marrow transplant and childhood cancer survivors are underway or beginning. Until such studies are done, it is too early for senolytics to be used outside of clinical trials.