New vaccine works against multiple fungal infections

Latest study shows efficacy against yeast infections in mouse model, paving the way for clinical trials in people

University of Georgia

A vaccine developed by University of Georgia researchers successfully protects against and treats vaginal yeast infections in mice, according to a newly published study.

This is the newest application of the vaccine, which was previously shown to protect against the three most common fungal pathogens in four preclinical animal models, including nonhuman primates. These three fungi are responsible for more than 80% of fatal fungal infections.

The latest finding helps clear the way for the vaccine to enter clinical trials. If successful, the vaccine will be the first to prevent pathogenic fungal infections, which the World Health Organization considers one of the top threats to public health.

"We can’t just keep … trying to make new drugs to fight fungal infections because we’re going to lose.” —Karen Norris, College of Veterinary Medicine

“The thing that’s keeping researchers like me up at night is increasing antifungal drug resistance,” said Karen Norris, lead author of the study and a professor of immunology and translational biomedicine in the UGA College of Veterinary Medicine. Norris is also the CEO and founder of NXT Biologics, the company behind the vaccine. “It’s not a prediction. We’re living it right now.

“And we can’t just keep swinging away and trying to make new drugs to fight fungal infections because we’re going to lose. These organisms are always adapting to resist new drugs.”

The vaccine, named NXT-2, aims to fill that gap, preventing fungal infections before they happen and reducing the need for antifungal medications by doing so.

First clinical trial to target yeast infections; later trials to focus on life-threatening infections

The vaccine will first be tested in women with recurrent yeast infections, also known as recurrent vulvovaginal candidiasis or RVVC.

Caused by a type of candida fungus, the condition affects hundreds of millions of women globally. It also costs billions of dollars in health care visits, medication and lost productivity each year in the U.S. alone.

“RVVC is not life-threatening, but it is miserable,” Norris said. As many as one in 10 women develop the condition during their lifetime, suffering three or more yeast infections per year. “This is a huge need.”

The current treatment protocol relies on one class of drug, increasing the likelihood that the medication will develop resistance and be harder to treat going forward. They also can’t be used during pregnancy and don’t prevent future infections.

"I believe this vaccine will do the most good in people who are at high risk for highly dangerous, life-threatening infections.” —Karen Norris

Most of the women suffering from recurrent yeast infections are young and otherwise healthy, which makes them an ideal population for a Phase 1 clinical trial.

The results will inform future trials in more vulnerable patient populations, such as transplant recipients and cancer patients, two groups that are particularly vulnerable to life-threatening fungal infections, also covered by the vaccine.

“I’ve had a physician say to me, ‘I have patients that I get through stem cell transplants for their cancer treatment, and then they get aspergillosis. I often don’t have adequate treatment for that,’” Norris said. Pulmonary aspergillosis is a serious complication of this treatment and up to half those patients will die from the infection.

“That’s where I believe this vaccine will do the most good: in people who are at high risk for highly dangerous, life-threatening infections.”

Fungal infections: A growing public health threat

Fungal infections are most commonly seen in people with immune disorders, including those with uncontrolled HIV or impaired immunity from therapies like chemotherapy or anti-inflammatories.

But previous research from Norris, postdoctoral fellow Emily Rayens and the College of Public Health’s José Cordero showed that the at-risk population has expanded in recent years.

That study showed people with diabetes; chronic obstructive pulmonary disease (or COPD); or co-infections such as COVID-19, tuberculosis or flu are likewise at higher risk of developing fungal infections.

As drug resistance grows and infections become more difficult to treat, prevention becomes more critical, Norris said.

This is the first fungal vaccine that has shown broad, cross-protective antifungal immunity in multiple animal models, which bodes well for future clinical trials.

Published in Nature’s NPJ Vaccines, the study was co-authored by the UGA Center for Vaccines and Immunology’s Daniel Wychrij, Taylor Chapman, Whitney Rabacal, Hubertine Willems and Kwadwo Oworae. Additional co-authors include Emily Rayens, a doctoral graduate from UGA’s Department of Infectious Diseases, and Brian Peters of the University of Tennessee.

Journal

npj Vaccines

DOI

10.1038/s41541-025-01171-4

Article Title

Protective efficacy of the pan-fungal vaccine NXT-2 against vulvovaginal candidiasis in a murine model

Article Publication Date

17-Jun-2025

ERC grant will support the placement of tens of thousands of previously unknown fungi in the evolution tree

Estonian Research Council

Leho Tedersoo, Professor of Mycorrhizal Studies at the University of Tartu, has received the Advanced Grant from the European Research Council to systematise and describe members of the 95% majority of previously unclassified microscopic fungi, and other eukaryotic organisms not yet included in the current tree of life system. Using the kingdom Fungi as an example, a new system for DNA-based classification of organisms can then be created.

More than 160,000 species of fungi have been described worldwide, which can be assessed based on their morphological characteristics. It is estimated, however, that there are two to three million species in the fungi kingdom, many of them invisible to the naked eye. The majority of these live in the soil, playing crucial roles in ecosystem functioning, such as decomposing organic matter and supporting plants in nutrient uptake. There are also some species whose spread we want to restrict, as they live as parasites in plants or animals.

The current methods for describing and communicating fungal species have proven insufficient. As a result, a lot of them are not covered in the tree of life that describes the evolution and taxonomic relationships of living species. What has not been described is really hard to protect or, in the case of pathogens, to prevent systematically.

Undescribed biodiversity

Tedersoo’s research group, which operates in the Mycology and Microbiology Center at the University of Tartu, focuses on microscopic soil fungi. Over the past 15 years, they have collected tens of thousands of soil and leaf samples during global biodiversity research. In the last five years, they have also taken water and household dust samples, the DNA information of which often indicates that there are species and deep phylogenetic lineages that have never been described yet.

“This can partly be explained by the fact that the samples came from some tropical region where no one had collected them before. However, very common microscopic fungi often occur in many places around us but cannot be cultured in a Petri dish and, therefore, cannot be suitably described using classical taxonomy methods. This leads to a direct need to devise a new system that would allow us to talk about, distinguish and systematise non-cultivable microscopic fungi,” said Tedersoo.

Tedersoo’s group plans to apply the latest methods of molecular biology and genomics, which make it possible to obtain information necessary for species identification even from a single cell, if necessary. This is particularly useful in environmental monitoring, where environmental DNA samples are increasingly used to provide insights into, for example, the species living in a body of water based on the genetic material found in a water sample. In this field, a good partner is the European Molecular Biology Laboratory (EMBL) in Germany, where novel methods are used and members of Tedersoo’s research group are trained to build relevant laboratory capabilities in Tartu for future collaboration.

Revolution in species description

Based on the obtained DNA data, researchers are working out principles for a new taxonomic system. The question is how to include the existing taxonomic data in the new system to avoid the emergence of two parallel approaches to species description.

Tedersoo acknowledges that the task is a very time-consuming , but he remains hopeful that within the next ten years, it will be possible to describe representatives of very large and widespread groups of microscopic fungi at the phylum, order, or family level, which would help establish the basic structure of the fungal evolutionary tree.

The Advanced Grant received from the European Research Council is intended for leading top-level scientists who have achieved outstanding research results over the last ten years. The project “Phylogenetic taxonomy and classification of fungi” runs until the end of February 2030 and its budget is €3.3 million.

A fungal origin for coveted lac pigment

Indian Institute of Science (IISc)

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Lac insects surrounded by their resin seen attached on their host plant
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Credit: Sourajyoti Pal

The colourful pigment extracted from the lac insect may actually be produced by a symbiotic yeast-like organism living inside the insect, a new study by researchers at the Indian Institute of Science (IISc) has found. The team showed that the yeast-like organism exclusively harbours genes coding for key ingredients in the pigment synthesis pathway.

With its rich red colour, the lac pigment is a prized commodity used not only in food colouring, textiles, and dyes, but also in handicrafts and folk art. “For thousands of years, India has been a key producer of the lac pigment,” says Shantanu Shukla, Assistant Professor in the Department of Developmental Biology and Genetics (DBG), IISc, and corresponding author of the study published in the Proceedings of the National Academy of Sciences.

The lac insect grows on certain trees (like the “Flame of the Forest”), drinks its sugary sap, and secretes a sticky resin called shellac. It also makes a bright red compound called laccaic acid, which is used to make the pigment. How the insect produces laccaic acid has remained a source of mystery. For decades, scientists have unsuccessfully hunted for genes coding for its synthesis in the insect’s genome. “The pathway for the pigment production was not very clear,” Shukla says.

One of the key ingredients required for laccaic acid synthesis is an amino acid called tyrosine, which the insect cannot make on its own or source from the tree sap. Such missing ingredients are usually supplied by symbiotic bacteria or fungi that live inside insect bodies and secrete these molecules in exchange for housing.

The team sequenced the entire bacterial and fungal microbiome of the insect and zeroed in on two possible candidates: a bacterium belonging to the Wolbachia genus and a yeast-like fungus. Previous studies by other researchers had hinted at the presence of the fungus but had not identified it or sequenced its genome.

In the current study, the team found that neither the insect nor the bacterium carried the genes needed to make tyrosine and other components of the pigment pathway. But the yeast-like organism did – it carried the entire set of genes needed for laccaic acid production. This includes genes coding for various enzymes which catalyse the production of aromatic molecules that are the building blocks of laccaic acid.

One of the key challenges was growing lac insects that lacked the yeast-like organism in order to tease out the latter’s role, says Vaishally, first author and PhD student in DBG. “The fungus is uncultivable, and the insects themselves can’t survive outside their host plant in an artificial culture system. So, all our experiments had to be done using host plant-reared insects, which made it difficult,” she adds.

“What is very peculiar about the fungus is that … it is actually inside the insect’s oocyte [egg cell],” Shukla says. The fungus floats around in the insect’s haemolymph – the equivalent of animal blood – and as soon as the oocyte matures, it latches on to and enters the oocyte, and gets transmitted to the offspring that emerges from the oocyte. “This type of ‘vertical transmission’ is striking,” Shukla adds.

When the team sprayed a fungicide on the lac insects, they found that pigment production reduced, and the insect also shrank in size. This suggests that the insect likely relies on the fungus for other nutrients missing from its diet as well – a dependence shaped over millions of years of evolution.

“The yeast-like organism is central to this story in a way because fungal symbionts are not well understood in insects,” Shukla says. “This study highlights the importance of fungi in insect evolution.”

Lac insects surrounded by their resin seen attached on their host plant

Credit

Sourajyoti Pal