Annual Report on the Status of SOCK FIP and FIP Research at UC Davis and Possible Directions for Future FIP Research

Niels C. Pedersen, DVM PhD

We had hoped that in 2023 one or more antivirals for cats would be legalized. With the exception of a few countries outside the US, this has not happened. Still, there is hope that studies being conducted at the University of California, Davis and elsewhere around the world will help advance conditionally and/or fully approved human drugs such as Remdesivir, Molnupiravir and Paxlovid for use by veterinarians. Even if drugs are approved for use in animals, drugs marketed for human use are not ideal because they must be purchased at the price set for humans. Therefore, the unapproved market will remain the main source of cheaper antivirals for many years to come. However, SOCK FIP appreciates the efforts of countless cat owners and lobbying industry and government agencies to allow the use of effective antivirals for cats. These efforts have had varying degrees of success in many countries outside the US.

FIP research at UC Davis in 2023 supported by SOCK FIP contributions

2023 continues to support SOCK FIP and feline coronavirus research at UC Davis, and we couldn’t do it without the help of many donors. Two ongoing research projects receiving SOCK FIP funding are of particular interest. The first project involves testing antiviral drugs and is led by Drs Krystle Regan and Brian Murphy. Patients and owners were drawn from across the US. The first study compared two antiviral drugs in cats with wet FIP to test cure rates with either oral GS-441524 or Remdesivir (Gilead). This study, which was published, showed that oral Remdesivir worked as well as oral GS-441524. So if Remdesivir gets full approval in the United States, veterinarians can safely prescribe it to cats with wet FIP. Other studies comparing GS-441524 and Remdesivir in cats with dry FIP and Molnupiravir (Merck) in cats with wet FIP have also been completed. The results of these studies should be published in early 2024. The latest study involving Paxlovid (Pfizer) was recently fully approved and widely available in the United States, and if it proves to be a safe and effective treatment for cats with FIP, it will a third human antiviral drug to treat FIP that may one day be used by veterinarians. Drs Regan and Murphy also used their field test cases to study the causes of death during the first two weeks of treatment. This population represents up to 10 % treated cases worldwide. Necropsies showed the existence of serious complicating diseases, which often included bacterial sepsis, often with highly resistant organisms to antibiotics, as well as serious heart disease. More work is needed to determine the nature of the heart disease and how much of it may be pre-existing disease and how much is caused by the FIP virus.

The second major research project focused on the prevention of FIP is implemented by Dr. Patricia Pesavento, one of our veterinary pathologists, and her research team, which includes veterinary microbiologist Terza Brostoff, biomedical engineer Randy Carney, immunologist Dennis Hartigan O’Connor, and lab technician Ken Jackson. Their study involves the development of an mRNA vaccine against a portion of the nucleocapsid protein that is common to virtually all known feline coronavirus isolates. The theory is that an immune response to this protein, compared to the spike protein commonly used in COVID-19 vaccines, will protect cats exposed to the common enteric form of feline coronavirus from developing FIP. This would be analogous to the protection against severe and chronic forms of COVID-19 reported with mRNA vaccines. Team Dr. Pesaventa developed a vaccine based on ideal manufacturing parameters and tested it for safety and efficacy in a rodent model. The development of this mRNA vaccine will only be a first step as it will need to be further tested in a limited number of cats as a prelude to much more extensive field testing in larger populations of cats such as breeding stations or temporary/rescue stations experiencing ongoing cases of FIP.

Areas of future FIP research

The discovery of a cure for FIP does not end the need for further FIP research. We hope that veterinary scientists from around the world who are still active in academia and industry will consider some of the other promising areas of research. Such studies cover all aspects of FIP pathogenesis, from the basic enteric coronavirus, which is enzootic in virtually all healthy cat populations and exists in the lower intestinal tract, to mutant forms that have acquired the ability to infect monocytes/macrophages in and outside the abdominal cavity. The exact nature of immunity to feline coronaviruses, both the minimally pathogenic enteric form and the highly lethal form causing FIP, needs to be clarified. We know that immunity to both intestinal and extraintestinal forms of the virus is weak, short-lived and susceptible to weakening by internal and external stressors. Immunity to enteric coronavirus appears to involve locally produced antibodies, whereas immunity to FIP-causing mutant viruses involves more systemic lymphocyte-mediated (cellular) immune responses. Accurate knowledge of the strengths and weaknesses of both types of immunity will be essential for all future vaccine development efforts. Will you prevent FIP by attacking underlying enteric coronavirus infections or by attacking FIP-causing mutants when they emerge?

There is a great need to develop tests that can accurately determine when a cat has been cured by antiviral therapy. We know that some cats can heal in as little as 4-6 weeks, while others need up to 12 weeks. We suggest 12 weeks of treatment because this gives the maximum cure rate, but we know that some cats will be treated for an unnecessarily long time. The only current way to tell when a cat is cured is to stop the treatment and see if the disease returns. Regular complete blood counts and basic serum biochemistry are useful in conjunction with physical health indicators in monitoring and managing treatment, but return to normal test values and general health do not guarantee that treatment will not relapse. On the contrary, the persistence of minor abnormalities in the blood and health status is not always a sign that there has been no cure and that it is necessary to increase the dosage or prolong the treatment. This is especially true for cats with neurological FIP, where blood test results and the status of neurological deficits do not always indicate a cure.

Although there is hope that even more effective antiviral drugs will be found in the future, the well-documented safety and efficacy profiles of current drugs leave little room for further improvement. However, drug resistance is currently being observed in some cats. What is known about how drug resistance develops in chronic infections such as HIV/AIDS should be applied to FIP. The most effective way to combat drug resistance in HIV/AIDS is to combine two or more antivirals with different mechanisms of action before resistance develops.

It appears that some strains of feline coronavirus may be more neurotropic than others. A penchant for infecting the central nervous system can be developed by specific mutations in enteric strains of the coronavirus that are enzootic in the environment or by mutations that occur as part of the FIP biotype. The role of the blood-brain barrier and the apparent compartmentalization of immunity between the central nervous system and the rest of the organism are other areas that require study.

Most cat owners are currently aware of the large outbreak of FIP occurring on the island of Cyprus. It is still uncertain whether this outbreak qualifies as epizootic (epidemic) or enzootic (endemic). Preliminary research suggests that the outbreak is linked to closely related isolates of FIP virus serotype 2 (similar to canine coronavirus). It is clear that for cats in all parts of the world, whether this outbreak is related to the spread of the virus from cat to cat (ie, an epizootic disease) or to factors promoting the disease in the environment (ie, an enzootic disease) is important. The worst possible scenario is a panepizootic disease like COVID-19. Hopefully, researchers in Cyprus, the UK and elsewhere will be able to resolve the nature of this outbreak as quickly as possible.