Lessons from horticulture: Pioneering the first antifungal vaccine
In the arid soil of the southwestern United States, as well as in parts of Mexico and South America, a potentially deadly fungal organism threatens the health and lives of both humans and animals. Coccidiomycosis, also called Valley fever or San Joaquin Valley fever, is caused by one of two fungal species: Coccidioides immitis (the most common organism in California) or Coccidioides posadasii (the most common organism outside of California).
The name “Valley fever” comes from one of the two most highly endemic areas for this area: the southern San Joaquin Valley in California (the other area is southern Arizona). But the affected geographical area is expected to grow as this organism spreads over the next few decades due to factors including climate change and increased construction activity.
Kicking up dust—and Coccidioides
The most common mode of infection is inhalation of the Coccidioides fungal spores that become airborne as soil and dust are disturbed. It is not contagious between animals, or between animals and humans.
As the organism makes its way down to the lungs, infected individuals can develop a fungal pneumonia, characterized by a harsh dry cough, lethargy, anorexia, and fever. This can happen anywhere from three weeks to three years after exposure.
While some cases will resolve without treatment, others can spread throughout the body, affecting the joints, skin, eyes, spine, and brain. In addition to infecting humans, Valley fever can cause significant disease in a variety of animal species, especially dogs, cats, nonhuman primates, llamas, and alpacas.
Dogs at 8x higher risk
David Bruyette, DVM, DACVIM, chief medical officer of Anivive Lifesciences, reports that the risk of Valley fever infection in dogs is about eight times higher than the risk in humans. This is thought to be due to dogs’ closer proximity to the ground and their tendency to investigate the ground with their noses, making them more predisposed to inhalation of fungal spores.
Additionally, most infected dogs require treatment, and more dogs will have disseminated disease (about 25% of cases) by the time they are diagnosed when compared to humans (about 1% of cases).
The result of severe infection in dogs can include treatment costs reaching $15,000–$20,000, the need for lifelong treatment, and sometimes euthanasia due to poor prognosis and/or poor response to treatment.
Although the risk of infection for humans is lower than for dogs, there is still risk of serious disease, lifelong complications, and mortality in infected humans (especially the immunocompromised).
Developing a Valley fever vaccine for dogs
For both animals and humans, the only method of prevention available up until now has been avoidance, which is largely impractical for those who live in endemic areas. Bruyette reports that “pet owners and veterinarians have been looking for a safe and effective vaccine for decades,” but previous efforts have been unsuccessful.
Anivive Lifesciences, however, is poised to bring the first fungal vaccine to market for any species. This vaccine will protect susceptible dogs from Valley fever infection.
The story of this novel vaccine starts with horticulture researchers studying the virulence factors of a fungal organism that infects corn crops. These researchers discovered that deleting a particular gene (cps1) in the Cochliobolus species would render the fungal pathogen avirulent and therefore incapable of causing disease in the corn plant.
Researchers at the University of Arizona then determined that the Coccidioides organism contains the same gene—and determined that deleting it had the same avirulence effect. Importantly, this gene-deleted organism is still antigenic, meaning it still stimulates an immune response. This made it a great candidate for use in a live fungal vaccine.
Based on these findings, Anivive has partnered with the University of Arizona and the National Institutes of Health to develop a Valley fever vaccine for dogs. This vaccine is a live, cps1-deleted strain of Coccidioides posadassii that has been shown in initial studies with mice and dogs to stimulate immunity against both C. immitis and C. posadassii without causing the disease.
Protection against the disease has been determined through challenge studies, where vaccinated dogs who were then experimentally exposed to the disease had much lower infection rates. Serology is not helpful in this case, however, because the vaccine works by stimulating a cellular response and not a humoral (antibody) response. The benefit here is that vaccinating a dog will not interfere with current diagnostic antibody testing of dogs suspected of having the disease.
Possible vaccine access by end of 2023
Edward Robb, DVM, MS, DACVIM (Nutrition), who leads the vaccine program, states that Anivive is currently finalizing the studies that demonstrate the stability of the vaccine when stored in the refrigerator. They are also finishing the “reversion to virulence and shed/spread studies” in laboratory dogs. These studies look for any evidence that a live vaccine will revert to virulence inside the dog’s body and that the vaccinated dog can shed spores that might infect other dogs. The results will give the United States Department of Agriculture (USDA) the information needed to authorize field studies in pet dogs in four sites around the US.
If the USDA approves the field studies, and if those yield results similar to the initial trials, it’s possible that veterinarians may have access to a canine Valley fever vaccine by the end of 2023.
Other animals in Anivive’s sights for Valley fever vaccine development include cats and zoo animals housed in endemic areas. Anivive also owns the rights to the human vaccine as well, and they are currently working to find the appropriate human vaccine manufacturer with whom they can partner to help provide protection for susceptible people.
If there’s a theme in this story, it’s one of partnership. Experts in different but related fields come together, share their results, and find ways to apply their knowledge to solve additional problems. This type of collaboration will undoubtedly help scientists find solutions for many other challenges that extend across the divide between humans, animals, and the environment.
Anivive information on Valley fever
CDC information on Valley fever
Free On-demand Valley fever CE from Anivive
Join the Anivive advocates to help advocate for this vaccine with the USDA
Emily Singler, VMD, writes this monthly column for NEWStat exploring One Health and the human-animal bond. She is a 2001 graduate of Penn State University and a 2005 graduate of University of Pennsylvania School of Veterinary Medicine. She has worked in shelter medicine, private practice, and as a relief veterinarian. She currently works as a veterinary writer and consultant and has her own blog, www.vetmedbaby.com.
Photo credit: ©Aleksandr Zotov E+ via Getty Images Plus