Temperature-stable TB vaccine is safe and provokes immune response

By Brian Doctrow, Ph.D., National Institutes of Health.

An experimental tuberculosis vaccine that can be stored at room temperature was safe and provoked an immune response in a Phase 1 clinical trial.

If proven effective in larger trials, the vaccine could make tuberculosis prevention more accessible to those most at risk.

Mycobacterium tuberculosis bacteria in lungs.The bacterium that causes tuberculosis, Mycobacterium tuberculosis, typically affects the lungs, but can also affect other parts of the body. Left untreated, the disease can be deadly.

Tuberculosis (TB) is a contagious disease caused by infection with Mycobacterium tuberculosis bacteria. It spreads through the air when a person with TB disease of the lungs or throat coughs, speaks, sings, or even just breathes.

While TB typically affects the lungs, it can also affect other parts of the body, including the kidney, spine, and brain. Without proper treatment, the disease can be deadly: it killed 1.6 million people worldwide in 2021 alone.

Only one vaccine is currently available for preventing TB, and it is only partly effective. A class of improved vaccines, called adjuvanted subunit vaccines, have shown promise in clinical testing. But so far, all need to be kept refrigerated, which can be costly and difficult in low-resource areas. Unfortunately, these are often the same areas where the TB burden is greatest. A vaccine that could be stored at room temperatures would be much easier to deliver where it’s needed most.

A team of researchers led by Dr. Christopher Fox at the Access to Advanced Health Institute (AAHI) in Seattle developed a freeze-dried, temperature-stable form of an adjuvanted subunit vaccine. The vaccine can be stored at human body temperature for three months.

The team conducted a Phase 1 clinical trial, funded by NIH, to determine the vaccine’s safety and ability to provoke an immune response. Forty-eight participants received either the temperature-stable or a previous, non-temperature stable form of the vaccine. Both vaccines were administered in two injections eight weeks apart. Results appeared in Nature Communications on March 6, 2023.

Both versions of the vaccine were safe and well-tolerated, with similar patterns of adverse events. Common problems included pain at the injection site, fatigue, headache, and muscle ache. All adverse events were mild to moderate, and none were severe or serious.

Participants in both groups produced antibodies in response to the vaccine. But those receiving the temperature-stable form made more than those receiving the non-temperature stable one. Participants receiving the temperature-stable vaccine also had more antibody-producing cells in their bloodstreams. In addition, both vaccine versions elicited immune system T cells, which help recognize and kill pathogens.

The results suggest that the temperature-stable version of the vaccine is as safe and provokes as strong an immune response as the previous version. If proven effective in larger clinical trials, the vaccine could have a major impact on global TB prevention.

“Equitable access to vaccines has been significantly impeded by [refrigeration] requirements and, as observed with COVID-19, no one is safe until everyone is safe,” says AAHI CEO and study co-author Dr. Corey Casper.