I’m Amélia Houana, a Medical Doctor passionate about research and public health. I am currently collaborating in the Tuberculosis and HIV/AIDS area at the Manhiça Tuberculosis Initiative (MTBI), an initiative of the Manhiça Health Research Centre (CISM). Since October 2022, I have been working on research related to tuberculosis vaccines that could provide stronger and longer-lasting protection across all age groups and against all forms of TB. The only tuberculosis (TB) vaccine currently in use is Bacille Calmette-Guérin, commonly known as BCG which was developed in the early 20th century by Albert Calmette and Camille Guérin. BCG works by stimulating the immune system to protect against TB. It contains weakened live bacteria that are closely related to Mycobacterium tuberculosis, the bacterium that causes TB in humans. When BCG is administered, it prompts the immune system to produce a response that can recognize and destroy Mycobacterium tuberculosis if a person is exposed to it in the future. It’s the most effective preventive tool, but the only one available in more than 100 years of research and it has several limitations.
Effectiveness and Challenges
1. Variable Protection: BCG’s effectiveness varies widely depending on geographic location and population. It tends to offer better protection against severe forms of childhood TB, such as TB meningitis and miliary TB, than against pulmonary TB (the most common form).
2. Limited Duration: Protection provided by BCG is not lifelong. It typically wanes over time, which means individuals vaccinated as infants may lose some or all of their immunity by adulthood.
3. TB Eradication Challenges: Several factors contribute to why BCG has not been able to eradicate TB worldwide:
Complexity of TB: Mycobacterium tuberculosis has complex mechanisms to evade the immune system and can remain dormant in the body for years before causing active disease.
Global Health Inequities: TB is closely linked with poverty, malnutrition, overcrowding, and inadequate healthcare access—all of which complicate efforts to control and eliminate the disease. Drug-Resistant TB: The emergence of drug-resistant strains of Mycobacterium tuberculosis further complicates treatment and control efforts
The hurdle to developing a new vaccine
That’s why we need to develop new vaccines, but it’s a complex and rigorous process that involves several stages, each presenting its own set of challenges which can be summed up as:
1. Exploratory Stage:
Research and Discovery: Scientists identify antigens that can provoke an immune response against the target pathogen (e.g., virus, bacterium).
Preclinical Studies: Vaccine candidates are tested in laboratory and animal models to assess safety, immunogenicity (ability to provoke an immune response), and efficacy.
2. Clinical Development:
Phase 1 Clinical Trials: Small groups of healthy volunteers receive the vaccine to evaluate the safety and immune response.
Phase 2 Clinical Trials: Expanded to hundreds of volunteers to further assess safety, immunogenicity, and optimal dosage.
Phase 3 Clinical Trials: Involves tens of thousands of volunteers to confirm efficacy, monitor adverse reactions, and compare the vaccine against a placebo or existing standard.
3. Regulatory Review and Approval:
Regulatory Authorities: Vaccine developers submit extensive data to regulatory agencies (e.g., FDA - U.S. Food and Drug Administration, EMA -European Medicines Agency ) demonstrating safety, efficacy, and manufacturing quality.
Approval Process: Agencies review data and conduct independent evaluations to determine if the vaccine meets safety and efficacy standards.
4. Manufacturing and Quality Control:
Scaling Up Production: Developing processes to manufacture large quantities of the vaccine while maintaining consistency and quality.
Quality Control: Ensuring every batch of vaccine meets stringent safety and potency standards.
5. Post-Marketing Surveillance:
Monitoring: Continual monitoring of vaccine safety and effectiveness once it’s released to the public.
Adverse Event Reporting: Rapid identification and response to any safety concerns that arise post-approval.
The IPREV-TB study and the M72 clinic trial
The whole TB community has long worked to develop and approve new vaccines. There are promising results from centers all over the world. The Global Tuberculosis Report 2022 lists 14 candidate TB vaccines in the clinical development phase, including 8 in phase 2b-3 trials. In Mozambique, we are playing our part too. At MTBI we are currently working on two studies:
The Gates MRI TBV02-E01 study, also known at CISM as "IPREV-TB," where I am the Clinical Coordinator, is a TB epidemiological research project. Supported by the Bill and Melinda Gates Foundation, the IPREV-TB study focuses on assessing the interferon-gamma release assay (IGRA) positivity and building capacity to conduct a tuberculosis (TB) vaccine efficacy study in populations with a high burden of TB.
The IPREV-TB study is a preparation for a project that will start soon: the M72 clinical trial, also funded by the Bill and Melinda Gates Foundation. The M72 clinical trial represents a significant step forward in TB vaccine research, particularly promising due to its previous efficacy results in phase 2b (about 50% efficacy).
M72 is a phase 3 clinical trial - This phase involves a large-scale evaluation of the vaccine’s safety, efficacy, and immunogenicity in a diverse population. The trial will be conducted across 60 sites in 7 countries globally, reflecting its multinational scope and collaboration. Approximately 20,000 participants will be recruited worldwide, highlighting the trial’s size and significance in evaluating vaccine efficacy across diverse populations.
In Mozambique, CISM and INS (Instituto Nacional de Saúde), will participate as sites in the M72 Clinical Trial. Each site is tasked with recruiting 500 participants, contributing to the overall recruitment goal and ensuring representation from Mozambique in the global study cohort. Mozambique is a high TB burden setting, and unfortunately, still figures among the 30 countries with the highest rates of Tuberculosis worldwide. This enhances the trial’s diversity and relevance by including populations with varying genetic backgrounds and TB epidemiological profiles.
With the M72 clinical trial we aim at confirming the results we have observed in phase 2b results. In case of positive phase 3 results we also hope the World Health Organization (WHO) recommends the M72 vaccine’s inclusion in national immunization programs, potentially transforming global TB control efforts.
Transforming TB control efforts globally
Developing a new tuberculosis vaccine holds significant promise in radically changing TB control efforts globally by reducing incidence, curbing drug resistance, improving public health outcomes, and promoting health equity. It represents a critical advancement in the fight against one of humanity's oldest and deadliest infectious diseases.
As a doctor and young researcher, it’s a fantastic opportunity for me to collaborate on promising projects that could forever change the course of tuberculosis.
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