Why are there no vaccines for fungal infections?

Unfortunately, our understanding of immunity to fungi lags far behind our understanding of bacterial or viral infections. There are currently no vaccines available for any fungal infection, but several groups around the world are working towards designing and getting them approved for use in clinics.

The fungal vaccine currently nearest to the finish line is called NDV-3A. It is designed to boost immunity against Candida and prevent vaginal thrush (yeast infection), which will be of great comfort to people suffering from recurrent thrush (4+ infections per year).

Current efforts to produce an Aspergillus vaccine are mainly aimed at preventing invasive aspergillosis, which kills around 200,000 people per year worldwide. Many of these infections could be prevented if we had a way to vaccinate high-risk patients before starting medical treatments that lower their immunity (for example chemotherapy, transplants, strong steroids). However, it is very difficult for a person who already has an existing immunodeficiency to mount an effective immune response.

Efforts are also being made to develop a ‘pan-fungal’ vaccine, which would protect against many fungal pathogens at once.

 

What aspergillosis vaccines are in the pipeline?

Several approaches to designing an Aspergillus vaccine have been tried and are starting to achieve promising results in mice. Some researchers have tried injecting purified (recombinant) single proteins, while others have tried using complex mixtures made by fragmenting Aspergillus cell wall matter.

Earlier this year, staff at the Center for Vaccines and Immunology (University of Georgia, USA) tried using a recombinant protein called AF.KEX1, which is naturally found on the surface of Aspergillus cells. Vaccinated mice showed a good antibody response and grew smaller amounts of Aspergillus in their lungs. Importantly, they were less likely to die even if their immune systems were suppressed using corticosteroids.

 

Will they be used to prevent CPA / ABPA in future?
Even after a vaccine for invasive aspergillosis has been approved, more work will be needed to find out whether it is also effective in preventing CPA and/or ABPA. It is much harder to predict who is at risk of developing chronic forms of aspergillosis because they are so rare even among people who have a known risk factor – most people with COPD do not develop CPA, and most people with asthma do not develop ABPA. This make it very hard to decide who should be vaccinated. It also makes it difficult to recruit enough of the right patients to run a meaningful clinical trial.

 

So how long?

As with many medical conditions, a prevention is better than a cure. But this is a long-term goal and it is impossible to predict with any accuracy when an Aspergillus vaccine will be available to patients.

We might hope to see some early-stage trials in humans in the next 3-5 years, but there is no guarantee that any of the current candidates will be effective or safe enough in humans to justify larger trials or be rolled out in clinics.

On the other hand, the COVID-19 pandemic has generated an enormous amount of public interest and new technologies for vaccination. Multiple COVID-19 vaccines were developed and brought to the public on a timescale that could scarcely be imagined even just 5 years ago. We may find that the vaccine development landscape changes beyond recognition in the near future and brings the prospect of an Aspergillus vaccine closer than we thought.

 

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