Tuberculosis (TB) is an airborne disease caused by infection with Mycobacterium tuberculosis (M.tb). It is the world’s deadliest infectious disease and one of the top 10 leading causes of death overall. In 2019, an estimated 1.4 million people died as a result of TB disease (WHO Global Tuberculosis Report 2020).
Low- and middle-income countries account for 97% of reported TB cases, according to the World Health Organization (WHO). Thanks in large part to the increased availability of HIV treatment in these countries, the number of TB cases is down globally. But there were still about 10 million new cases of TB disease in 2019, according to the WHO, and the emergence of drug-resistant TB is a growing global public health crisis. The only licensed TB vaccine, the bacille Calmette-Guérin (BCG) vaccine, was developed 100 years ago and is still widely used to prevent TB disease in infants and children. However, its efficacy is variable and there is currently no vaccine that is effective in preventing TB disease in adults, who, along with teens, are most at risk for developing and spreading TB. Development of new TB drugs and more effective vaccines remains a top priority.
Now, after decades of research, there is a renewed optimism for TB vaccines. In 2018, a Phase II trial conducted in South Africa showed that revaccinating adolescents with the BCG vaccine they received as infants significantly reduced occurrence of sustained TB infections. Another Phase IIb efficacy study, conducted by IAVI in collaboration with GSK, showed that the GSK TB vaccine candidate M72, administered along with the company’s AS01E adjuvant, protected against active pulmonary TB disease in adults latently infected with TB bacteria, with an overall vaccine efficacy of 50%. These findings, if confirmed in follow-up studies, would represent a breakthrough in the quest to develop an effective TB vaccine. These trials could also provide valuable insights that scientists can use to design even better vaccine candidates.
The way forward for TB vaccine candidates
Advancing a vaccine candidate to a next stage of development requires complex decision-making for vaccine developers and funders. This is particularly true for TB vaccines — the field lacks correlates of protection for vaccine efficacy as well as a predictive animal model, and the funding environment is restricted.
In order to support and facilitate decision-making in TB vaccine development the TuBerculosis Vaccine Initiative (TBVI) and IAVI, with input from the research community, international policymakers, technical agencies, and funders, established the TB Vaccine Development Pathway. The Pathway is a methodology and interactive online tool that provides a structured development path and gating criteria for candidate TB vaccines.
The Pathway has been developed on behalf of the Global TB Vaccine Partnership, an alliance of organizations that aim at making novel TB vaccines a reality. The Pathway is funded by the Bill & Melinda Gates Foundation and is revised every two years to incorporate scientific and technical progress, as well as input from users. The most recent update was published in October 2019.
Fast facts about TB and HIV
TB primarily affects the lungs, though the bacteria can infect any organ. According to the WHO, almost one-quarter of the world’s population has latent TB infection and is at risk of developing active TB disease. The situation is even more dire for people living with HIV, for whom TB disease is the leading cause of death. In addition, people living with HIV:
- Accounted for almost 8.2% of the cases of TB disease reported globally in 2019; 73% of these cases occurred in Africa.
- Accounted for about 14% of all TB-related deaths reported globally in 2019.
- Develop TB disease at a rate 20 times higher than the rest of the population.
- Experience poorer health outcomes from TB disease, even when treated.
- Face an increased mortality risk from multi-drug resistant TB if diagnosis is delayed.
For a full picture of the global burden of TB, see the WHO's 2020 Global Tuberculosis Report, published in October 2020.
IAVI and TB vaccine development
IAVI is currently partnering in clinical trials of three novel TB vaccine candidates.
- A Phase Ib/IIa dose-defining safety and immunogenicity study (A-050) of the live, attenuated vaccine candidate MTBVAC in South Africa. MTBVAC, produced by the Spanish pharmaceutical company Biofabri, is the only live, attenuated M.tb. vaccine candidate, and it is being compared with BCG in adults with and without latent TB infection.
- A Phase II study (A-055) involving adults in South Africa and Tanzania. Statens Serum Institut’s H56 TB protein vaccine candidate, in combination with the IC31® adjuvant, developed by Valneva, is being evaluated in a trial sponsored by Statens Serum Institut and IAVI South Africa NPC (formerly known as Aeras Global TB Vaccine Foundation NPC) to see if it reduces the rate of recurrent TB disease in HIV-uninfected adults already successfully treated for pulmonary TB disease.
- A Phase III study (priMe, NCT04351685) taking place at sites in Gabon, Kenya, South Africa, Tanzania, and Uganda, where there is a high TB and HIV burden. Serum Institute of India Pvt. Ltd. (SIIPL) and Vakzine Projekt Management GmbH (VPM) are sponsoring this study, which will evaluate the efficacy and safety of the vaccine candidate VPM1002 in comparison to BCG for the prevention of TB infection in HIV-exposed and HIV-unexposed newborn infants. The vaccine candidate is a recombinant version of BCG, the only licensed TB vaccine. Genetic material from another bacterium is incorporated into BCG with the goal of enhancing the immune response.