A vaccine created by University of Georgia researchers to battle multiple life-threatening fungal infections is successful in achieving protective immunity in pre-clinical animal models while also maintaining the biodiversity of the gut microbiome, according to a new study.
This is the first study to evaluate a vaccine's effect on naturally occurring fungal and bacterial communities in the gut, known as the microbiome.
The vaccine, called NXT-2, could be the first to protect against and potentially treat pathogenic fungal infections.
But not all fungi are bad. In fact, strains of Candida and Aspergillus can be found in healthy gut microbiomes. It's only when their growth goes unchecked that they can pose a threat.
The findings confirm that the vaccine provides protection against pathogenic fungi while not significantly altering the resident fungi or bacteria populations in the gut.
"We have previously shown that the NXT-2 vaccine is very good at eliminating or controlling harmful fungal infections," said Karen Norris, corresponding author of the study and a professor in UGA's College of Veterinary Medicine. "It was important to determine whether that immune response would disrupt the balance of beneficial microbes in the gut.
"This study shows that there are not significant alterations following successful immunization with NXT-2."
Fungal infections kill millions and cost billions each year
The vaccine has already proven effective against the three most common fungal pathogens in four pre-clinical animal models. These three fungi are responsible for more than 80% of fatal fungal infections.
It's also shown efficacy against Candida auris, a type of yeast that spreads easily, particularly in healthcare settings, and can lead to severe illness or even death. C. auris is also often resistant to multiple antifungal medications, prompting the Centers for Disease Control and Prevention to label it an urgent public health threat.
Fungal infections kill millions each year and cost billions in healthcare expenses. They also double hospitalization costs, double the length of hospital stays and double the risk of death in hospitalized patients, according to a previous UGA study.
There are no effective vaccines to protect against fungal infections.
Preserving the balance of the organisms that comprise the gut microbiome is critical. And these results support the further advancement of the first broadly protective fungal vaccine.
Karen Norris, College of Veterinary Medicine
Current treatments can't keep up as fungi become increasingly resistant to medication. And some antifungal drugs have been shown to alter the populations of nonharmful fungi and bacteria in the gut.
Previously considered a threat largely reserved to the immunocompromised, pathogenic fungal infections are increasing among the general population.
People with diabetes, chronic obstructive pulmonary disease or co-infections such as the flu are all at higher risk of developing fungal infections, according to previous research from Norris, former UGA postdoctoral fellow Emily Rayens and the UGA College of Public Health's José Cordero in 2022.
New study is one of few to focus on vaccine effects on gut microbiome
Studies on how vaccines affect the gut microbiome remain limited. But research suggesting that the microbiome plays a key role in the immune response and efficacy of vaccination is growing.
The composition of the gut microbiome varies greatly from person to person. Even the same person can experience shifts in bacteria and fungi over time.
This study is the first comprehensive analysis of both bacterial and fungal communities following antifungal vaccination.
"Preserving the balance of the organisms that comprise the gut microbiome is critical," Norris said. "And these results support the further advancement of the first broadly protective fungal vaccine."
The gut microbiome of nonhuman primates closely resembles that of humans, enabling the researchers to examine the effect of NXT-2 on natural levels of bacteria and fungi in the digestive tract.
The study suggests that the vaccine's antibodies target pathogenic fungi in invasive infections while leaving innocuous fungi populations alone.
Published by Mycology, the study was co-authored by the College of Veterinary Medicine's Kwadwo Oworae, Whitney Rabacal, Anna Hu, Daniel Wychrij, Emily Rayens, Taylor Chapman and Justin Bahl, professor of epidemiology and biostatistics.
