Tuberculosis (TB)
Tuberculosis (TB) is a contagious disease primarily targeting the lungs, caused by specific bacteria. It transmits through the air when individuals with the infection cough, sneeze, or spit. Our company is well-equipped to address your therapy and vaccine development requirements in Tuberculosis.
Introduction to Tuberculosis
Tuberculosis (TB), caused by bacteria from the Mycobacterium tuberculosis complex, is one of the oldest known human diseases and continues to be a major global health issue. In 2022, TB was the second leading cause of death from a single infectious agent, after COVID-19. The global incidence rate for TB was about 133 new cases per 100,000 people annually, with over 10.6 million new cases and 1.6 million deaths reported that year.
Fig. 1 Shows an estimated number of incident TB cases and TB deaths (in millions) from 2000 to 2017. (Natarajan, A., et al., 2020)Pathogenesis of Tuberculosis
The pathogenesis of tuberculosis (TB) involves the initial inhalation of Mycobacterium tuberculosis into the alveoli, where it is phagocytosed by alveolar macrophages. Inside the macrophages, the bacteria evade destruction by inhibiting phagosome-lysosome fusion and inducing alveolar macrophage necrosis through ESAT-6 secretion. This process leads to local inflammation and recruitment of additional immune cells, facilitating further spread of the bacteria to lymph nodes and potentially leading to systemic dissemination.
Fig. 2 Ciclo infectivo de M. tuberculosis. (Cardona, P.J., 2018) Molecular Diagnosis Development of Tuberculosis
Polymerase Chain Reaction (PCR)
PCR is a technique that amplifies specific DNA segments, widely used for the rapid diagnosis of TB. PCR can detect MTB within hours, even with low bacterial loads in samples such as sputum. dehydrogenase (pLDH).
Line Probe Assay (LPA)
LPA detects the presence of MTB and drug resistance mutations through PCR amplification followed by hybridization with specific oligonucleotide probes. LPA has been endorsed by the WHO for detecting resistance to rifampicin and isoniazid.
Whole Genome Sequencing (WGS)
WGS is a next-generation sequencing technology that reads the entire genome of microorganisms at high throughput. WGS can identify all relevant mutations and provide functional categorization, offering significant advantages over other methods.
Vaccine Development of Tuberculosis
Therapeutic TB vaccines act as immunotherapeutic adjuncts to chemotherapy by modulating the host's anti-TB immunity. These vaccines are administered either to enhance therapy during active disease, to prevent recurrence or relapse after standard therapy, or to prevent the reactivation of latent tuberculosis into active disease.
Vaccines being developed to improve therapeutic outcomes in active TB include M. vaccae, RUTI, MIP, and AERAS-402. Those designed to prevent relapse and reinfection include the H56 and ID: GLA-SE subunit vaccines, RUTI, BCG, the recombinant BCG vaccine VPM1002, and MVA-85A. These candidates are currently in phase 2 or 3 clinical trials in TB individuals during or after the completion of therapy.
Fig. 3 Overview of selected therapeutic TB vaccines in the clinical pipeline. (Bouzeyen, R. and Javid, B., 2022)
Our Services
Our company adopts a collaborative approach, partnering closely with clients to create tailored and innovative therapy strategies for Tuberculosis. We offer comprehensive support throughout the entire development process, ensuring effective and customized solutions.
Platforms of Tuberculosis Therapy Development
Animal Models for Tuberculosis
We have extensive experience in creating and utilizing animal models that faithfully mimic the disease traits and therapeutic reactions of Tuberculosis. These models enable us to evaluate the safety and effectiveness of prospective therapeutics with precision.
| Mouse Models | Advantages | Disadvantages |
|---|---|---|
| Inbred "resistant" (C57BL/6, Balb/c) | Consistent results, use of gene knock-out mice, extended studies, kinetics, indicators of protection, and immunological resources. | Absence of human-like pathology (e.g., liquefaction, fibrosis) and relevant Mtb-induced cell types. |
| Inbred "susceptible" (C3HeB/FeJ, 129Sv, I/St, DBA/2) | Study of pathology, necrotic granulomas, susceptibility markers, and drug testing. | Few knock-out mice are available, and there is no model for the chronic or latent stages of the disease. |
| Outbred | Genetic variability, microbiome diversity. | Housing inbred and pathogen-free mice is challenging, affecting reproducibility |
| Collaborative cross (CC) lines | Genetic diversity and gene association studies. | Low reproducibility, costly, and resource-intensive. |
| Humanized mouse | Representation of human-specific cell types or effector functions. | Costly, variable, technology-intensive, and highly sensitive to attenuated strains. |
In addition, we offer a range of comprehensive animal model services that concentrate on specific signaling pathways and molecular targets.
If you are interested in our services, please contact us as soon as possible for more information.
References
- Natarajan, A., et al., "A systemic review on tuberculosis." Indian J Tuberc, (2020). 67(3): p. 295-311.
- Cardona, P.J., "Pathogenesis of tuberculosis and other mycobacteriosis." Enferm Infecc Microbiol Clin (Engl Ed), (2018). 36(1): p. 38-46.
- Bouzeyen, R. and Javid, B., "Therapeutic Vaccines for Tuberculosis: An Overview." Front Immunol, (2022). 13: p. 878471.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.