Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Biomedicines, Год журнала: 2025, Номер 13(2), С. 439 - 439
Опубликована: Фев. 11, 2025
Background/Objective: Finding new targets to attenuate Mycobacterium tuberculosis (Mtb) is key in the development of TB vaccines. In this context, plasma membrane P-type ATPases are relevant for mycobacterial homeostasis and virulence. work, we investigate role copper-transporting ATPase CtpA Mtb Methods: The impact deletion on Mtb's capacity overcome redox stress proliferate mouse alveolar macrophages (MH-S) was evaluated, as well its effect immunogenicity. Moreover, influence pathogenicity a (BALB/c) model progressive examined. Results: We found that MH-S cells infected with wild-type (MtbH37Rv) or mutant strain (MtbH37RvΔctpA) showed no difference bacterial load. However, same under copper activation (50 µM CuSO4) impaired replication strain. Furthermore, MtbΔctpA an inability control reactive oxygen species (ROS) induced by PMA addition during infection. These results, together high expression Nox2 mRNA observed Mtb∆ctpA at 3 6 days post-infection, suggest potential overcoming infection conditions. addition, MtbΔctpA-infected BALB/c mice survived longer significantly lower lung loads tissue damage their lungs than MtbH37Rv-infected mice. Conclusions: This suggests involved virulence it may be target attenuation.
Язык: Английский
Процитировано
1
Vaccine X, Год журнала: 2025, Номер unknown, С. 100615 - 100615
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
Vaccines, Год журнала: 2024, Номер 12(12), С. 1397 - 1397
Опубликована: Дек. 12, 2024
Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance immune evasion mechanisms employed Mycobacterium (Mtb). Although pulmonary TB remains primary focus research, MDR-TBM introduces unique challenges in diagnosis, treatment, patient outcomes. The effectiveness current treatments frequently compromised poor CNS penetration anti-TB drugs necessity for prolonged therapy, which often considerable toxicity. This review explores potential cytokine-based adjunct immunotherapies MDR-TBM, addressing balancing pro-inflammatory anti-inflammatory signals within CNS. A prospective role glutathione, not only reducing oxidative stress but also enhancing host defenses against Mtb’s strategies. Furthermore, development vaccines aimed at upregulating glutathione synthesis macrophages represents promising strategy bolster response improve treatment By integrating innovative vaccine approaches into management, this proposes comprehensive that targets Mtb directly while supporting modulation, with enhance outcomes reduce related adverse effects. We underscore urgent need research adjunctive therapies immunomodulatory strategies more effectively combat MDR-TBM.
Язык: Английский
Процитировано
3
Frontiers in Tuberculosis, Год журнала: 2024, Номер 2
Опубликована: Июль 19, 2024
Although Bacillus Calmette-Guérin (BCG) vaccine, the only licensed vaccine against tuberculosis (TB), is most widely used worldwide, TB second leading global killer from a single infectious agent responsible for over one million deaths annually. With increasing threat of emergence drug-resistant TB, there intense research toward better and more efficacious vaccines TB. Indeed, has blossomed in recent years: demonstration sterilizing immunity Mycobacterium (Mtb) challenge non-human primates, potential benefit BCG revaccination humans, phase IIb with ~50% efficacy developing active disease. Consequently, several are set to begin 3 trials 2024, new candidates have entered 1 including mRNA-based vaccines. However, despite enthusiasm, no known correlates protection antigens that induce protective incompletely defined, overreliance on Th1 cytokine production as an “absolute” measure increasingly debatable. In this perspective, I highlight milestones Vaccine remaining challenges propose suggestions future considerations.
Язык: Английский
Процитировано
0
Vaccines, Год журнала: 2024, Номер 12(8), С. 876 - 876
Опубликована: Авг. 2, 2024
Tuberculosis (TB) is an ancient global public health problem. Several strategies have been applied to develop new and more effective vaccines against TB, from attenuated or inactivated mycobacteria recombinant subunit genetic vaccines, including viral vectors. This review aimed evaluate patents filed between 2010 2023 for TB vaccine candidates. It focuses on vector-based strategies. A search was carried out in Espacenet, using the descriptors "mycobacterium tuberculosis" classification A61K39. Of 411 preliminarily identified, majority were related with 10 based vector platforms selected this study. Most of identified belong United States China, a concentration patent filings 2013 2023. Adenoviruses most explored vectors, common immunodominant
Язык: Английский
Процитировано
0
Vaccines, Год журнала: 2024, Номер 12(12), С. 1335 - 1335
Опубликована: Ноя. 27, 2024
Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide, necessitating the development more effective vaccines. Nanoparticle-based adjuvants represent promising approach to enhancing tuberculosis vaccine efficacy. This review focuses on advantages nanoparticulate-loaded vaccines, emphasizing their ability improve antigen delivery, safety, immunogenicity. We discuss various types nanoparticles unique physicochemical properties that contribute improved delivery sustained immune activation. Additionally, we highlight nanoparticle-based in inducing strong cellular humoral immunity, stability, reducing adverse effects. Finally, address current challenges future perspectives application these novel adjuvants, potential transform TB strategies ultimately better global health outcomes.
Язык: Английский
Процитировано
0
Journal of Pharmaceutical Sciences, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
0