Development of Cryptococcus Vaccine Against Invasive Fungal Infections

Inventor(s):  Chaoyang Xue, Amariliz Rivera

Awarded:  January 2021

Summary:  Invasive fungal infections constitute a rising and lethal threat to patients due to increased populations with immunodeficiency and are difficult to treat. There are very limited options of antifungal drugs with only three main drug classes, and currently no vaccines in clinical use to combat fungal infections. Hence, there is a clear unmet medical need to develop a vaccine. Our project tackles this important clinical problem by developing a broad-spectrum fungal vaccine to control the deadly invasive fungal infections that account for over 1.5 million deaths each year globally. 

Our vaccine candidate is based on a Cryptococcus neoformans strain lacking a F-box protein (Fbp1) that is required for protein degradation. Our data demonstrate that mice vaccinated with the heat-killed fbp1∆ mutant cells (HK-fbp1) can provide protection against several major invasive fungal infections, including Cryptococcus species, Aspergillus fumigatus, and Candida albicans. Its protection remains effective against Cryptococcus in CD4 T cell-depleted mice, a condition mimicking AIDS patients. The vaccine protection is also effective against Aspergillus infection in neutropenic mice. Our preliminary data also showed a potential therapeutic value of our vaccine. A therapeutic vaccine may have advantage more than the small molecule antifungals and will likely reduce side effects and the overall treatment cost.

Market Applications: 

• There is no fungal vaccine in clinical use. Therefore, the market is wide open.
• This is the first vaccine candidate in development that showed cross protection against multiple fungal infections, leading to an increased market size.
• The vaccine may be used prophylactically for risk populations (e.g. patients with HIV/AIDS, cancer chemotherapy, solid organ transplantation, and people who travel to regions with local outbreaks or where fungal diseases are prevalent).
• The vaccine may also be used as a therapeutic vaccine to treat patients with cryptococcosis, alone or in combination with antifungal drugs.