On the third floor of the University of Montana’s Skaggs Building, researchers work on the building blocks of a better vaccine for one of the world’s most lethal infectious diseases — tuberculosis.
Earlier this fall, the National Institutes of Health awarded a $12.3 million contract to the university’s Center for Translational Medicine and its partners to develop a novel adjuvant for use in a tuberculosis vaccine. Adjuvants are substances that improve vaccine effectiveness by boosting immune response.
The five-year award follows UM’s successful $13 million NIH contract to develop compounds targeting an immune response, said Jay Evans, director of the Center for Translational Medicine and co-leader of the project. Researchers will develop those compounds into an adjuvant to be used in vaccine clinical trials in three to five years.
“The development and clinical evaluation of safe and effective adjuvants is urgently needed for the advancement of vaccines to combat the ongoing threat of bacterial and fungal infections, including tuberculosis, pertussis and others,” Evans said in a press release.
While the new contract is for adjuvant development for a bacterial or fungal pathogen, it’s highly likely the work will lead to a clinical trial for a TB vaccine because researchers are using the disease as a model and because of the high medical need, Evans told Montana Free Press.
Tuberculosis is an infectious disease caused by a bacteria that most often attacks the lungs but can affect other parts of the body. An estimated quarter of the global population has been infected with TB bacteria, and about 5% to 10% will eventually develop tuberculosis, according to the World Health Organization. Tuberculosis is preventable and curable but can be fatal without treatment.
While not common in the United States, 1.3 million people died from tuberculosis in 2022, according to WHO. An effective vaccine is needed for areas like Southeast Asia and Africa where the disease is endemic, or regularly occurring, Evans said.
The available Bacille Calmette-Guérin (BCG) vaccine does not always prevent people from getting tuberculosis and does not prevent an asymptomatic infection from advancing into the lungs, according to the organization.
A vaccine candidate still undergoing clinical trials was found to be 50% effective in reducing pulmonary tuberculosis in adults, according to WHO. The initial results are an improvement over the BCG vaccine, but 50% efficacy isn’t ideal, Evans said.
“Our goal is to do better,” he said.
SIMPLER AND SAFER
A vaccine targeting a bacterial or fungal infection like tuberculosis needs to generate a certain immune response to best fight these types of infections, Evan said. The UM team’s research started by looking at how the tuberculosis bacteria elicit that response and found a compound on the surface of the bacteria is key, he said.
However, that compound is “really complex” to make in a lab and has too much toxicity to use in a potential vaccine, Evans said. The chemistry team instead makes compounds do the same thing but are simpler and safer, he said.
Under the previous contract, researchers spent years screening, testing and identifying compounds that fit the right mold, Evans said. In the next five years, they will work on improving the compound structure and exploring how to formulate the best one into a vaccine that’s safe and easy to deliver to people, he said. That includes making sure the compounds are stable and could be stored in a refrigerator, or in an ideal world, at room temperature, Evans said.
“Especially for a vaccine for something like TB, in the parts of the world where it’s endemic, there are problems with the cold chain and getting it to where people need it,” he said.
The Center for Translational Medicine has extensive experience developing adjuvants, including work on a COVID-19 vaccine in 2020.
“Especially for a vaccine for something like TB, in the parts of the world where it’s endemic, there are problems with the cold chain and getting it to where people need it.”
Jay Evans, director of the Center for Translational Medicine
“It’s what we do, what we’ve done for a long time and what we’re good at,” Evans said.
A small group of approximately 40 people on the translational medicine team will work on this project along with other contracts, Evans said. Over the five years, 20 to 30 scientists will be involved, including researchers at the University of Chicago, the Texas Biomedical Research Institute and Missoula-based Inimmune Corp., a biotechnology company. UM graduate and undergraduate students will also participate.
“It gives them a view into what a job in this field will be like if they stay in research or go into the industry,” Evans said. “I don’t think a lot of students get that opportunity. In their time, they may see it move into a setting to hopefully help people.”
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