World Tuberculosis Day – Raising awareness for the initiatives to combat and eradicate Tuberculosis.
Many people think that tuberculosis is a disease of the past and has been eradicated from society. However, this is far from reality. According to the WHO, a total of 1.6 million people died from TB in 2021, with 10.6 million people contracting the disease worldwide.
What is Tuberculosis?
Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, which is transmitted from person to person through the air, usually when someone with active TB coughs or sneezes. The disease is primarily known to affect the lungs but can also spread to other parts of the body, such as the brain, spine, and kidneys.
When someone inhales air containing TB bacteria, the bacteria can enter their lungs and cause an infection. Most people who are exposed to TB bacteria do not develop active TB because their immune system is able to control the infection. However, some people’s immune systems are not able to control the bacteria, causing them to develop active TB. Active TB can cause a range of symptoms including coughing, fever, night sweats, weight loss and can also damage the lungs, causing scarring and reducing lung function. In severe cases, TB can be fatal.
In Synexa’s home country South Africa, TB poses a significant public health problem. According to the World Health Organization (WHO), South Africa has one of the highest burdens of TB in the world, with an estimated 301,000 new cases of TB reported and 58,000 deaths in 2020. Furthermore, TB and HIV co-infection is common in South Africa, as HIV weakens the immune system and makes individuals more susceptible to TB infection.
One of the challenges of treating TB is that the bacteria can become resistant to antibiotics, known as multidrug-resistant TB (MDR-TB). In some cases, TB can also become extensively drug-resistant (XDR-TB), meaning it is resistant to most antibiotics. MDR-TB and XDR-TB are more difficult to treat and can be more severe than non-resistant TB. This is why finding a solution through vaccines has become more important than ever.
The current state of TB research
The only licensed TB vaccine, Bacille Calmette-Guérin (BCG), provides protection against pulmonary and other severe forms of TB in infants and young children. Since its introduction in 1921, it has saved tens of millions of lives but was not able to contain the global TB pandemic as it does not prevent infection with or transmission of mycobacteria. There has been some effort in evaluating new uses of the BCG vaccine. Using new routes of administration (IV versus IM) has shown some promising results in pre-clinical models and revaccinating adolescents with a booster dose of BCG vaccine has been shown to significantly reduce latent TB infections in adolescents.
A new generation of TB vaccines is therefore urgently needed to achieve prevention of infection and prevention of disease development. Several vaccine candidates are currently in late-stage (Phase 2b–3) clinical development. These vaccines are following different approaches including live attenuated or killed TB bacteria, and protein antigen (subunit) vaccines, either as adjuvanted recombinant proteins or virally vectored.
Promising results were obtained in a Phase 2b trial testing M72/AS01E, which is comprised of two recombinant Mtb antigens (Mtb32A and Mtb39A) in AS01 adjuvant. This vaccine candidate was able to protect latently Mtb-infected adults from developing active TB disease with an efficiency of approximately 50%.
Spurred on by the success and rapid development of COVID-19 vaccines, researchers are now developing TB vaccine candidates based on mRNA technology. The experience gained from the accelerated development of COVID-19 vaccines may lead to more TB vaccine candidates soon joining the development pipelines. The potential of mRNA technology, together with the WHO’s mRNA Technology Transfer Hubs raises hopes that soon new vaccines will be produced in Low-Middle Income countries where the need for these vaccines is greatest.
The recent progress in TB vaccine development has also provided an opportunity to identify immunological correlates of protection, in particular specific T cell and antibody signatures, that could serve as biomarkers for the successful selection of candidate TB vaccines and accelerate and reduce the cost of human efficacy trials.
Earlier this week, we caught up with Andreas Soares, Global Head of Cell Biology and Natalie Strickland, Global Head of Translational Science, to share their thoughts on TB research and what can be done to continue progress to eradicate this disease in the future:
Andreia Soares, Global Head of Cell Biology
“On this World TB Day, we reflect on the devastating impact that TB continues to have on individuals, communities, and global health. At Synexa, we are committed to contributing to the development of new TB vaccines and supporting global efforts to eradicate this disease.
My contribution to TB research began during my PhD at the University of Cape Town, where I conducted an in-depth analysis of T cell-mediated immunity to determine when to boost Bacille Calmette Guérin (BCG)-specific immunity following vaccination of newborns. This work provided novel insights into the development of BCG-specific immunity in humans and the optimization of future TB prime-boost vaccination strategies. As a post-doctoral fellow, my research predominantly focused on innate and adaptive immune responses and mechanisms of immunopathogenesis in the context of HIV and HIV-TB co-infection. At Synexa, I am proud to continue contributing to the global fight against TB and remain dedicated to making a meaningful impact in the lives of those affected by this disease.”
Natalie Strickland, Global Head of Translational Science
“I first became involved in TB research as a postdoctoral fellow at the Institute of Infectious Disease and Molecular Medicine (IDM) at the University of Cape Town. My research centred around TB and HIV co-infection and the role of the adaptive immune system in the pathogenesis of TB. We used Mycobacterium tuberculosis (Mtb)-specific MHC Class II tetramers to examine polyfunctionality, activation and exhaustion in CD4+ T cells primed to recognise Mtb antigens in different HIV-TB co-infection cohorts. As a South African scientist working at Synexa, I am particularly passionate about contributing to research that will ultimately lead to effective vaccines and treatments to improve the quality of life of those affected by this pandemic.
Our team’s expertise in cell biology, flow cytometry, and ELISpot allows us to design and execute assays that provide valuable insights into the immune response to TB vaccines. By leveraging our capabilities, we can accelerate the development of effective TB vaccines and move one step closer to eradicating TB worldwide.”
Sample Access for Translational Research and Assay Development and Validation
Synexa Life Sciences has five laboratories worldwide including one in Cape Town, South Africa. We have excellent working relationships with infectious disease clinicians and TB-focused research organizations to access samples for us in translational research as well as assay development and validation work.
Sources:
- https://www.who.int/news-room/fact-sheets/detail/tuberculosis
- https://www.afro.who.int/health-topics/tuberculosis-tb
- https://www.gavi.org/vaccineswork/topics/making
- Scriba T, et al.; Seminars in Immunology 50 (2020) 101431
