Scientists at St. Louis University say they’ve found a better way to test vaccines developed to fight tuberculosis, a bacterial infection that sickens millions of people each year.
In a study recently published in the Journal of Infectious Diseases, SLU researchers and scientists from New York University and Emory University said they can use the Bacillus Calmette-Guérin vaccine against tuberculosis administered to babies and small children to mimic the disease to see how well other immunizations in development will work in adults.
“You're relying on the human response to understand what's important for immunity, what's important for vaccine development,” said Dr. Daniel Hoft, co-director of the SLU Center for Vaccine Development and co-author of the study. “We can screen new vaccines with this challenge model and determine which ones are best at inhibiting the organism from growing, and then focus on those that are best at doing that.”
While the BCG vaccine is given to young children to keep them safe from the most serious forms of tuberculosis, it becomes less effective as people age. TB is still one of the most common infectious diseases in the world. According to the World Health Organization, more than 1 million people died of tuberculosis in 2022. It’s particularly dangerous for people whose immune systems are compromised by HIV.
“It's a huge problem worldwide, that we haven't gotten anywhere close to conquering yet,” Hoft said. “So getting BCG at birth, or within the first month, does protect against those worst forms of the disease in the first five years of life. However, BCG has not made a dent in the overall prevalence of TB infection and disease. So we need better vaccines.”
Scientists can sometimes test immunizations by infecting people with bacteria or a virus in a controlled setting and see how they respond to a potential vaccine versus a placebo, Hoft explained.
But a human challenge study that infected people with the tuberculosis bacteria would be too dangerous, he explained. He said the study from SLU showed using the children’s BCG vaccine to mimic tuberculosis infection during a human challenge study could predict how well a patient would respond to a vaccine scientists are developing.
“We can look at people that have been given new vaccines, different vaccines, we can compare their ability to block the BCG growth after a challenge,” Hoft said. [We’ll] be able to prioritize which of the new vaccines are likely to work the best before needing to spend tens of millions of dollars and a decade or more on completing Phase 1 through Phase 3 [studies] for each candidate new TB vaccine.”
Human challenge trials can also show how men and women respond to viruses differently. Men, for instance, are more at risk of developing active tuberculosis infections, but scientists don’t know why.
The idea has merit, said Mike Frick, TB co-director of the Treatment Action Group, an international nonprofit that advocates for research into cures for infectious diseases.
“I think human challenge studies, especially ones of the type that is being used in St. Louis, which is using BCG in place of virulent TB itself, could prove to be a useful tool for developing TB vaccines,” he said. “But they will never replace, entirely, the main act, which will always be conducting randomized clinical trials in the field.”
There are already several tuberculosis vaccines being tested in randomized controlled trials in the field, Frick said.
One trial, for example, tests how well a potential vaccine suppresses tuberculosis in people who have latent TB or who test positive for the disease but do not yet have symptoms.
“It's not about developing a challenge model in isolation,” Frick said. “It's about developing a challenge model that is in conversation with other clinical work with other basic science research that's happening in the field. “
Human challenge trials can also show how men and women respond to viruses differently. Men, for instance, are more at risk of developing active tuberculosis infections, but scientists don’t know why.
