A Late-Stage Tuberculosis Vaccine is Making its Way Through Clinical Trials
Monday is World Tuberculosis (TB) Day, and a vaccine developed by the Gates Medical Research Institute is being studied in a phase 3 trial. If approved, the vaccine could potentially prevent pulmonary TB in adults and adolescents.
Monday, March 24, marks World TB Day, and TB incidence rates continue to pose a significant global health challenge. According to the World Health Organization (WHO), 10.8 million people contracted TB worldwide in 2023—an increase from 10.6 million in 2021. Additionally, the most recent numbers show TB resulted in 1.25 million deaths in 2023.¹
HIV and TB
Globally in 2023, there were an estimated 0.96 million new TB cases attributable to undernutrition, 0.75 million to alcohol use disorders, 0.70 million to smoking, 0.61 million to HIV infection, and 0.38 million to diabetes, according to the WHO. People with HIV are 16 times more likely to contract TB than those without HIV. TB remains the leading cause of death among people with HIV. In 2023, 161,000 people died from HIV-related TB.¹
The percentage of notified TB patients who had a documented HIV test result in 2023 was 80%, consistent with 2022 levels but up from 76% in 2021. The WHO African region has the highest burden of HIV-associated TB. In 2023, only 56% of TB patients known to be living with HIV were on antiretroviral therapy (ART).¹
TB Vaccine Candidate
The Gates Medical Research Institute (Gates MRI) has been developing a TB vaccine to address this global public health issue. The M72/AS01E TB vaccine candidate contains the M72 recombinant fusion protein, which is derived from 2 Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A), combined with GSK’s proprietary Adjuvant System AS01E. The Gates MRI, a nonprofit organization and subsidiary of the Gates Foundation, is sponsoring the trial, supported by funding from the Gates Foundation and Wellcome. GSK provides technical assistance and supplies the adjuvant component of the vaccine.²
This month marks 1 year since the launch of the phase 3 clinical trial. Over the past year, trial sites have been established at 54 locations across 5 countries: Indonesia, Kenya, Malawi, South Africa, and Zambia. If the vaccine is shown to be well-tolerated and effective in the ongoing trial, the M72/AS01E could potentially become the first vaccine to help prevent pulmonary TB in adolescents and adults—and the first new TB vaccine in over a century.
In the phase 2b trial, M72 demonstrated approximately 50% efficacy in reducing pulmonary TB in adults with latent TB infection—an unprecedented result in decades of TB vaccine research.²
Currently, the only approved TB vaccine, Bacillus Calmette–Guérin (BCG), has been in use since 1921. While effective in preventing severe childhood TB, it presents challenges for adults as it does not effectively prevent the disease in this population.
“Unfortunately, BCG does not protect—or offers minimal protection—against adult pulmonary TB. However, it prevents severe forms of childhood TB, which is why the World Health Organization recommends continued BCG use in high-burden settings,” said Alemnew Dagnew, MD, MSc, MVPCD, MPH, FRSPH, clinical development leader at Gates MRI. “The recommendation is to administer 1 dose of BCG as soon as possible after birth. It offers minimal or no protection against adult pulmonary TB but protects against severe forms of childhood TB,” Dagnew added.
Dagnew noted that if this vaccine proves effective in adults and adolescents, it could significantly improve prevention efforts in 2 populations in need of prophylaxis.
“If this vaccine works and prevents pulmonary TB in these 2 populations, it would have a huge impact on TB control efforts and the global push to stop TB transmission,” Dagnew said.
