Are New Tuberculosis Vaccines Really Needed

Due to the unexpected three-year increase in tuberculosis (TB) cases in the United States, there is a lot of attention focused on developing new preventive vaccines.

In the United States, the USAID Annual Tuberculosis Report to Congress, FY 2023, indicates about 8,300 individuals were diagnosed with TB in 2022, a 5% increase in the U.S. from the previous year, and global case notifications increased over the last year by 70%.

According to the World Health Organization (WHO), it is estimated that TB outbreaks caused 10.6 million people to contract TB in 2022, and 1.3 million died from the disease, many in India.

While 16 versions of the Bacille Calmette-Guérin (BCG) vaccine are currently in use, this century-old vaccine only provides around 50% protection against bacterial infection.

BCG vaccination does protect children against severe forms of TB, but it offers inadequate protection for adolescents and adults against the pulmonary form of the disease, which is primarily responsible for transmitting the TB bacterium, says the WHO.

Moreover, harmful TB bacteria can also impact the kidneys, spine, and brain.

Making effective TB vaccines accessible and affordable in areas of high disease burden is a long-term priority for the WHO.

To address this health need, the Bill & Melinda Gates Medical Research Institute (Gates MRI), a nonprofit organization and subsidiary of the Bill & Melinda Gates Foundation, is sponsoring a TB vaccine candidate study supported by the Gates Foundation and Wellcome funding.

The M72/AS01E vaccine candidate has been in development since the early 2000s.

In 2020, GSK plc partnered with the Gates MRI to further develop M72/AS01E.

If proven effective, the M72/AS01E vaccine candidate could be the first licensed TB vaccine in decades.

GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the vaccine for the Phase 3 trial, and will provide the adjuvant post-licensure should the trial be successful.

The Gates MRI has worked with various stakeholders, including communities around clinical trial sites, to guide the TB candidate vaccine to Phase 3.

At total capacity, this clinical trial (NCT06062238), which started on March 5, 2024, may include up to 20,000 participants, including people living with HIV, at up to 60 trial sites in seven countries.

To this end, the Gates MRI, GSK, Wellcome, and the Gates Foundation are working together to understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term sustainable access if the trial is successful.

“The launch of this pivotal Phase 3 trial demonstrates our commitment to harnessing the power of medical innovation to fight diseases like TB that are particularly devastating for low- and middle-income countries,” said Emilio A. Emini, Ph.D., CEO of the Gates MRI, in a press release on March 19, 2024.

“Clinical study of the vaccine will still require years, but our incredible partners in South Africa and elsewhere who have come together for the Phase 3 study share our hope in the vaccine’s potential.”

This study is anticipated to take up to five years (April 2028) to complete, which leads to regulatory approvals,

As such, worldwide collaboration and strong partnerships are a core component of planning for future access to the candidate vaccine, wrote Gates MRI.

“After dedicating over 20 years to developing this essential candidate vaccine, we at GSK are delighted that the Phase 3 trial is underway. Developing and ensuring access to global health products is complex. Still, our collaboration with the Gates MRI, Wellcome, and the Gates Foundation exemplifies the transformative power of leveraging diverse partners’ expertise to change the trajectory of challenging diseases, like TB, which place a huge burden on communities around the world,” commented Deborah Waterhouse, CEO, ViiV Healthcare and President, Global Health, GSK. 

The WHO estimated that over 25 years, at 50% protection, this new vaccine could save 8.5 million lives, prevent 76 million new TB cases, and save $41.5 billion for TB-affected households.

As of late March 2024, other TB vaccine candidates are conducting clinical research.