Seeking the last 20 million euros for a 100% Spanish vaccine to combat the deadliest disease in history

Spain is just steps away from marketing a new, more effective vaccine against tuberculosis , the world's deadliest infectious disease, killing more than a million people each year. The research, which began 25 years ago by Carlos Martín , a microbiologist and professor at the University of Zaragoza, will culminate in 2028 with the results of clinical trials in infants and adults. If these latest studies confirm the efficacy of the MTBVAC vaccine, the door will be opened to all the administrative and legal procedures for negotiating and authorizing licensing agreements so that other laboratories in countries with a high tuberculosis burden can produce and distribute it. Esteban Rodríguez, CEO of Biofabri , the Spanish biopharmaceutical company that has advanced industrial and clinical development over the past 17 years, is confident that the vaccine will be commercially available in 2029. It will not be sold over the counter, but rather, with the support of funders, will be produced in laboratories in Spain, India, and Brazil and distributed in low- and middle-income countries at affordable prices. To reach this scientific milestone in Spain, an additional €20 million in funding is still needed to develop the vaccine for infants.

Martín and Rodríguez are optimistic about the effectiveness of the new BCG vaccine, the only authorized injection to prevent tuberculosis, used for the last 100 years but based on a strain that causes the disease in livestock, not humans. They made this known this week to national and regional authorities, cooperation agencies, and others invited by the Ministry of Health to the Multisectoral Governance Group Meeting of the Tuberculosis Plan. They also shared progress and challenges in a meeting with three media outlets, including EL PAÍS.

The goal is for MTBVAC to be at least 50% more effective than BCG in preventing immunized individuals from developing the disease and, in turn, becoming carriers of the bacteria. It will consist of a single dose and can be transported under normal refrigeration, which facilitates logistics in hard-to-reach areas.

However, both have also acknowledged a financial gap exceeding €20 million for developing the vaccine for infants. "Organizations are focusing on funding where there is the greatest social impact [by cutting off the route of infection and because 90% of cases occur in adults]. That's why there haven't been any problems funding [the development of the vaccine] for adolescents and adults, but there have been problems with it for infants," explains the CEO of Biofarm. "Although the vaccine may be very effective, the results in them won't be seen for about 20 years."

Although the project already receives funding from the European Union, the Gates Foundation, Open Philanthropy, the NIH (National Institutes of Health), the German development bank KfW, the NGO IAVI, among others, resources are still needed for the final push. "In the baby project, the European Union funds 50%. The other 50% is still missing," comments the University of Zaragoza researcher. "Developing a pharmaceutical product is so expensive that you need a private company that wants to make a profit, or, if you don't want to make a profit, you need altruistic foundations or community funds," he adds.

Martín and Rodríguez are working to secure that funding. One of the objectives of meetings like the one with the Ministry of Health is to keep potential investors informed about the process. "It's not an over-the-counter vaccine, so there's no speculation or extra profit. That's why we're asking organizations to contribute to its development," says Rodríguez.

Tuberculosis has historically been the world's deadliest infectious disease. COVID-19 only took this position for three years. However, a year ago, the WHO warned that tuberculosis was once again the leading cause of death from infectious pathogens. In 2023, 10.8 million people contracted tuberculosis; of these, 1.25 million died . This is as if in 2023, 10 A350 planes had crashed every day, with no survivors.

The most serious aspect is that it primarily affects vulnerable populations. The Global Fund for HIV, Malaria, and Tuberculosis has even called it "the pandemic of the poor." In 2023, for example, two-thirds of new cases were concentrated in countries such as Bangladesh, China, the Philippines, India, Indonesia, Nigeria, Pakistan, and the Democratic Republic of the Congo.

The outlook is expected to worsen now that the United States, at the behest of President Donald Trump, has withdrawn from the World Health Organization (WHO) , suspended development funding, and dissolved the cooperation agency USAID . According to a study by the Barcelona Institute for Global Health (ISGlobal) , the suspension of US funding has already caused 25% of tuberculosis control agencies in 31 countries to halt their work.

In fact, the cuts also affected the Spanish vaccine project. "The trial in people with HIV in South Africa was funded by the NIH in the United States, and it wasn't completed with a certain number of individuals because there's no more funding," comments the microbiologist from the University of Zaragoza. However, he clarifies, the follow-up phase for vaccinated patients will be completed. The CEO of Biofabri, however, sees an opportunity here: "This shows that Europe has the power and can also do things."

The urgency of updating the vaccine

BCG (Bacillus Calmette-Guérin) has been used since 1920 and was developed from the Mycobacterium bovis strain, which causes tuberculosis in cows. It offers effective protection to infants and children against the most severe forms of the disease, but its effectiveness decreases in adolescents and adults, especially in cases of pulmonary tuberculosis, the most common and infectious form of the disease.

The Spanish vaccine, on the other hand, was developed from Mycobacterium tuberculosis , the bacterium that infects humans, and the gene that makes it contagious was removed through genetic engineering. The gene that creates the lipid layer that protects it and renders it "invisible" to the immune system was also removed. MTBVAC does not prevent infection—after all, a quarter of the world's population has the bacteria, according to the WHO—but it does prevent the development of pulmonary disease. Therefore, it is capable of breaking the chain of transmission.

MTBVAC is in the final phase of clinical trial efficacy studies. In the case of infants, Phase 3 trials began in 2022 and aimed to vaccinate 7,500 newborns in two African countries: half of the babies will receive MTBVAC and the other half will receive BCG. To date, more than 4,000 have been vaccinated, and the doses are expected to be completed by 2026. When they are completed, they will wait two years to verify whether the new vaccine is at least 50% more effective than the old formula in preventing children from developing the disease. “It is known that BCG is not 100% effective and that there is a 4% to 15% chance of developing the disease,” says Rodríguez, “therefore, a two-year period is allowed during which the first 50 cases are expected to appear.” Once these appear, it is verified which patients received the new vaccine and which received the old one. The biopharmaceutical company believes that the efficacy could be even higher than the 50% suggested by the initial data available.

In the case of adults, several studies are underway. A safety trial is being conducted in an HIV-positive patient, an efficacy trial is being conducted in 4,300 adolescents and adults in South Africa, Kenya, and Tanzania, and another in India with approximately 20,000 people. The clinical trial involves administering MTBVAC to some patients and a placebo to others. "These data would be considered sufficient to grant authorization," the developers emphasize.