Cordyceps infection in The Last of Us isn’t entirely real, but the lack of a fungal vaccine is

Second episode of HBO hit Last of Us It starts with a scene in Jakarta, Indonesia. It’s set in 2003, at the beginning of a (fictional) fungal pandemic that continues to destroy the world as we know it. After an expert in fungal biology evaluates the bodies of infected factory workers, she speaks quietly to military personnel who asked for her help in controlling the spread of the pathogen.

“There is no vaccine,” she says to his devastated face.

That was true in 2003 in the real world, and it is still true today. There are many vaccines against bacterial and viral diseases, but vaccines against fungal pathogens are not licensed for human use.

I didn’t give up on my efforts. Dennis Dixon, who heads bacteria and fungi research at the National Institutes of Health, said there has been decades of “continuous activity” aimed at developing fungal vaccines. However, a variety of scientific and economic challenges have pushed even more promising fungal vaccine candidates into the pharmacological trash can, harming human health.

The bacteria that cause zombies in the play are In many cases fictitious — at least as a human pathogen. In fact, the most serious fungal infections in humans affect immunocompromised people, such as untreated HIV-infected people and people undergoing cancer treatments, organ transplants, or taking medications for autoimmune diseases. give (These usually manifest as lung or bloodstream infections or meningitis, not zombification.)

However, some affect people with a normal immune system.Have you ever had a yeast infection or heard of Valley Fever? —And as the number of people taking immunosuppressants continues to grow, the global burden of fungal infections increases. is expected to upward climb and climate change accelerates.

The urgency to find a vaccine that protects against all fungal infections, or ideally one vaccine that protects against multiple types of fungal infections, is not new, but it is growing.

The question arises here: Why are there still no fungal vaccines in the head year of 2023? It highlights some peculiarities about the Kingdom of Life, which is already known for its telegenic weirdness.

Fungal vaccines help prevent many infections

Fungi are everywhere around us. It’s in the air we breathe, the surfaces we touch, and everywhere inside and outside our bodies. Still, as long as the immune system is functioning normally, most people are at low risk of fungal infections.

Perhaps the worst fungal infection likely to affect someone with a healthy immune system is Candida A genus that is technically a yeast (yes, yeast is a type of fungus, just like mushrooms and molds). affect. 1.4 million clinic visits annually only in the US.worldwide, estimated 138 million women Have four or more yeast infections per year.Other fungal infections common in healthy people Contains ringworm—this is a surprise! It is not caused by worms and is not caused by infected finger or toenails.

But fungal infections (including yeast infections) pose a far greater threat to people with compromised immune systems. 1.5 million dead every year. And in 2018, treating those infections cost him nearly $7 billion.

Fungal infections are most common in immunosuppressed people. This complicates the development and deployment of fungal vaccines.

The fact that most serious fungal infections primarily affect immunosuppressed people is big challenge As for developing vaccines to protect against them.

First of all, this complicates finding participants for clinical trials to test fungal vaccines.

To determine whether a vaccine works, scientists test promising vaccine candidates (usually prototypes that successfully prevent disease in ly infected animals) on large groups of humans. need to do it. We live in a world with medical ethics, so scientists can’t infect humans ly. Instead, we have to wait for the people in the trial to naturally encounter the disease they are trying to prevent.

The rarer the disease is, the more people scientists will need to track (and for longer periods of time) to look for it. It’s still relatively rare.

Karen Norris, an immunologist at the University of Georgia School of Veterinary Medicine who leads the team developing the fungal vaccine candidates, said her team “calculated” how long it would take to study a hypothetical vaccine targeting a single fungal infection. “It’s doable, but it will take years to enroll that many patients,” she said.

It is also difficult to design an effective vaccine for immunocompromised people who need it most. Effective vaccines work by training a person’s immune system to respond quickly to specific bacteria, but safely training a suppressed immune system is difficult.

In some cases, it is possible to predict immunosuppression. For example, when preparing to undergo chemotherapy or other immunosuppressive treatment. However, this is not always the case. People with HIV or those born with compromised immune systems are unable to plan or predict the state of their immune system.

This poses a major challenge for scientists who hope to ideally develop a vaccine that protects both those with healthy immune systems who remain immunosuppressed and those who have been initially diagnosed with immunosuppression. .

Another problem: Fungal cells are more like human cells than viruses and bacteria. That makes it more complicated to design vaccines that train the immune system to attack fungal cells rather than attack your own cells.

Economics may be the biggest barrier to fungal vaccines

Even if a vaccine is shown to be safe and effective in clinical trials, it does not mean that it will be mass produced and marketed. To do that, they also need the potential to make a profit: “Vaccine trials in this area are, to be honest, not very attractive to big pharma and others because they are not a common infection in many patients. not, ”he said Norris.

Even if vaccines prevent many illnesses and deaths in groups of people and reduce health care costs, those benefits go to individuals and the health system, not to the pharmaceutical companies that bear the costs of development and production. not. vaccination.

“For this to move forward, someone needs to develop that tough market,” Dixon said. A viable vaccine must not only be effective in preventing disease, but it must also be effective in large enough numbers of people to make large-scale production of the vaccine a worthwhile investment for pharmaceutical companies. I have.

Still, people are working on fungal vaccines, and there are some promising candidates

Regardless of disability, people have been working to develop fungal vaccines for decades.

To overcome the economic impossibility of developing vaccines that protect against only a few infections, some scientists are developing vaccines that protect against multiple fungal infections.

Norris’ group has developed prototypes that target three of the causative fungi. 80 percent For all infections in immunocompromised people: Candida, Aspergillus, and Pneumocystis. prototype Significant reduction in sickness and mortality with these infections in laboratory mice and primates.Various other candidates During study.

To date, three fungal vaccines have entered human clinical trials. In the early 1980s, a vaccine was tested to prevent infection. coccidioides — causative bacteria valley fever — infection did not decrease, and produced many side effects. Recently, two vaccination intended to prevent Candida (i.e. yeast) infections have shown good results in human safety trials. One of them showed promise in preventing recurrent vaginal infections in a small, placebo-controlled trial. Without proceeding to a comparative clinical trial, development stalled, Dixon said.

Norris said additional animal safety studies of her team’s prototype could take another year. If all goes well, the next step, safety testing in humans, will also take about a year. After that, it will take at least several more years of work before her team can produce a licensed vaccine at scale.

So while progress in fungal vaccines feels significant, it’s wise to have a firm grasp on the timeline for progress in the field, says Dixon. It will certainly take some time to figure out how to get it right and get to the finish line,” he said.