Journey back to 1921, a time before the internet, commercial air travel, and the discovery of penicillin. This was the year the bacillus Calmette Guérin vaccine, or BCG, was first administered to protect children against tuberculosis (TB). While those other technologies have evolved, BCG remains the only available TB vaccine.
Today, millions of infants receive BCG each year. But there’s a catch – BCG doesn’t prevent TB in adolescents and adults who are most at risk of spreading and developing the disease.
Since the 1990s, scientists around the world have led the charge to develop new vaccines to help end TB, and this may soon bear fruit.
What is TB?
TB, caused by infection with the airborne Mycobacterium tuberculosis (Mtb), has been with humanity for millennia. Once known as consumption, the white plague, and the romantic disease, better sanitation, drugs and BCG have helped control TB in many countries. Yet, TB remains the world’s deadliest infectious disease.
Since Mtb’s Nobel prize-winning discovery by Robert Koch in 1882, TB has claimed the lives of over 1 billion people – more than any other infectious disease.
In 2023 alone, 10.8 million people fell ill with TB and 1.25 million died. Most cases occur in 50 or so high burden countries, including several in Europe with the world’s highest rates of drug-resistant TB. Drug-resistant TB is rising globally, including strains resistant to even the strongest TB drugs.
An urgent need
New TB vaccines are set to have a transformative impact. And the need is growing more urgent. The recent dismantling of USAID upended TB services around the world, threatening to worsen outbreaks of untreatable disease and reverse decades of progress already strained by COVID-19.
“We need two things to make new TB vaccines a reality: greater support – including funding and political commitments – and close collaboration with affected communities to build trust and ownership so people can benefit from scientific progress,” said Paulina Siniatkina, TB survivor, artist, and activist.
The history of TB vaccines in a snapshot
French researchers Albert Calmette and Jean-Marie Camille Guérin created BCG from a weakened form of the bacteria that could safely induce immunity.
Since its introduction, billions have been vaccinated. BCG has been a mainstay of the WHO’s Expanded Programme on Immunization since 1974, while in Europe, most countries removed it from routine programmes as rates declined.
Despite the science being highly complex – Mtb is a sophisticated bug – years of ingenuity and perseverance means new vaccines may finally be within reach.
EU horizons for TB vaccines
As with COVID-19, we need multiple shots on goal. There are at least 16 novel candidates in clinical development worldwide; six are being developed by or in partnership with European institutions.
This includes MTBVAC, designed by Professor Carlos Martin from the University of Zaragoza in collaboration with the Institute Pasteur in 1997, and later in-licensed by Biofabri in Spain. in February 2025, MTBVAC entered the Phase 2b IMAGINE clinical trial in adolescents and adults in Kenya, South Africa, and Tanzania, in a trial sponsored by IAVI, a global nonprofit. An ongoing Biofabri-sponsored Phase 3 trial of MTBVAC in infants started in 2022.
In Phase 1 trials, Germany-based BioNTech is advancing two mRNA candidates (mRNA is a molecule that gives instructions to a cell on how to make different proteins) and Statens Serum Institute in Denmark is testing a novel protein subunit vaccine.
European funding has been critical, with supporters including the European & Developing Countries Clinical Trials Partnership (EDCTP), the European Commission, the European Development Bank, and the German and Norwegian governments.
Is the end in sight?
Crossing the finish line, however, requires scaled-up resources from European funders to support new and existing candidates, run necessary trials, and prepare for quick and equitable rollout. Global coordination, including through the WHO TB Vaccine Accelerator Council, is essential.
“The global community must be united in advancing TB vaccine candidates through increased investment in science, clinical trials, and licensure and anticipating the regulatory and logistical challenges of deploying new vaccines,” said Jeremy Farrar, Chief Scientist, World Health Organization. “Working with all partners, including scientists and affected communities, is absolutely critical to avoid delays in access to TB vaccines that can save millions of lives.”
Shaun Palmer is a Communications and Advocacy Specialist at IAVI, Netherlands.
