A new vaccine from the University of Georgia could be the first clinically approved immunization to protect against invasive fungal infections, a growing concern as resistance to antifungal drugs increases.
Fungal infections cause more than 1.5 million deaths worldwide each year and cost billions. They also double the cost of hospitalization, double the length of hospital stay and double the risk of death in hospitalized patients, according to a previous UGA study.
But there are currently no effective vaccines to protect vulnerable patients from fungal infections.
“There is a significant unmet clinical need for this type of prevention as well as treatment, particularly among immunocompromised individuals,” said Karen Norris, lead researcher of the new study and a professor at the College of Veterinary Medicine. “The patient population at risk for invasive fungal infections has increased significantly over the past few years.”
The experimental vaccine is designed to protect against the three most common fungal pathogens that are responsible for more than 80% of fatal fungal infections. The study tested the efficacy of the vaccine in four preclinical animal models, including nonhuman primates.
The researchers relied on various immunosuppressed models for the study, reflecting drug regimens similar to those of transplant recipients, people with HIV or cancer patients, some of the highest-risk human populations.
The vaccine was effective in developing protective antibodies in each of the models.
“Because it targets three different pathogens, the vaccine has the potential to be groundbreaking in invasive fungal infections,” said Norris, who is also a faculty member at the university’s Center for Vaccines and Immunology. “Plans are underway to develop the vaccine for a Phase I (human) safety trial.”
More people are at risk of yeast infections than just the immunocompromised
Fungal infections are most commonly seen in people with immune disorders, including those with uncontrolled HIV or compromised immunity from therapies such as chemotherapy or anti-inflammatory drugs.
But previous research by Norris, postdoctoral fellow Emily Ryens and Jose Cordero of the College of Public Health in 2022 showed that the at-risk population has increased in recent years.
This study showed that people with diabetes; chronic obstructive pulmonary disease (or COPD); or co-infections such as COVID-19, tuberculosis or influenza are also at higher risk of developing fungal infections.
The first line of defense is usually treatment with azoles, which are broad-spectrum antifungal drugs. But antifungal resistance is on the rise. As a result, yeast infections are becoming more difficult to treat, making prevention even more critical, Norris said.
The new vaccine targets the three most common causes of fungal infections: Aspergillus, Candida and Pneumocystis. Candida, in particular, is a growing concern in healthcare settings as different strains of the fungus become resistant to multiple drugs.
The vaccine showed broad, cross-protective antifungal immunity in the animal models, which bodes well for future clinical trials.
“This is an area that has been underdeveloped on the research front for a long time,” said Norris, who is also a Georgia Research Alliance Distinguished Scientist in Immunology and Translational Biomedicine. “These are very large populations of people who are at risk of invasive fungal infections, and although significant efforts have been made to develop vaccines, none have yet been approved. We believe this is a very strong candidate for a vaccine.”
Posted in PNAS Nexus, the study was co-authored by College of Veterinary Medicine Emily Ryens, Whitney Rabacal, Hubertin Willems, Gabriel Kirton, James Barber and Jarrod Musa; and Brandi Celia-Sanchez and Michelle Momany of the Franklin College of Arts and Sciences.
This research was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Georgia Research Alliance, and the University of Georgia Research Foundation.