Fluorescent antibody stain revealing the oval budding yeast cells of Candida albicans fungal organisms.
Currently, there are no licensed vaccines to prevent Candida or Staphylococcus aureus infections. With NIAID support, a vaccine candidate is being developed to protect against both infections.
Candida can cause fungal infections in humans. These infections, known as candidiasis, occur most frequently in individuals with risk factors such as weakened immune systems, certain medical conditions, and prior antibacterial use. In some cases, the fungus can escape from the gut to enter the bloodstream and cause more invasive disease known as candidemia, which is one of the most common bloodstream infections.
The bacterium S. aureus is one of the leading causes of healthcare-associated infections. Increased hospitalizations related to drug-resistant S. aureus infections have a significant human and economic impact, including increased mortality, longer hospital stays, and more complicated treatment.
A vaccine to prevent Candida and S. aureus infections could greatly benefit patients, especially those at high risk for infection such as people with weakened immune systems and individuals with high incidence of recurrent infections. NIAID has provided funding and support throughout basic research, discovery, and development of a vaccine candidate: NDV-3. In the early 1980s, NIAID funded studies at Harbor UCLA Medical Center to investigate how Candida adheres to and penetrates endothelial cells. This research led to the discovery of several adhesion proteins that conferred protection in mice. NDV-3 emerged as a lead vaccine candidate. NIAID preclinical services supported scale up, manufacture, and stability testing of this experimental Candida vaccine that also protects against S. aureus infection. In animal models, NDV-3 was found to be protective against several strains of S. aureus, including methicillin-resistant S. aureus (MRSA) strains and the newly emerging multi drug resistant Candida auris. NDV-3 is the first vaccine candidate to provide protective efficacy across kingdoms, as it works against fungi and bacteria.
In Phase I clinical trials sponsored by NovaDigm Therapeutics, the cross-protective vaccine was well tolerated, safe, and induced strong antibody and T-cell responses. The company also supported a Phase IB/IIA clinical trial evaluating the ability of NDV-3 to prevent vaginal candidiasis in women with recurrent vulvovaginal candidiasis. The investigational vaccine was found to be safe, well-tolerated, immunogenic and efficacious against recurrent vulvovaginal candidiasis. In collaboration with the Department of Defense, in 2018, NovaDigm Therapeutics launched a Phase II clinical trial testing NDV-3A’s ability to reduce colonization of S. aureus among military recruits. NDV-3A is a newer formulation of the NDV-3 vaccine.