Category: Projects

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Christmas greetings from SOCK FIP

with current information from Dr. Brian Murphy and Patty Pesavento

Original article: Season's Greetings from SOCK FIP

Funding from the SOCK FIP program has made great progress this year in our clinical trials at the UC Davis School of Veterinary Medicine. Drs Brian Murphy, Amir Kol and Krystle Reagan are leading three new clinical trials. Their goal was to identify FIP treatment strategies that are highly effective, legally available, and affordable. GS-441524, a drug closely related to remdesivir, has been found to be safe and effective in treating cats with naturally occurring FIP, but is not licensed in the United States. However, the FDA may soon grant full approval to remdesivir, allowing it to be legally sold for veterinary use. The study will include two treatment groups – one receiving oral GS-441524 and the other receiving oral remdesivir for comparison. Cats must be diagnosed with the wet form of FIP to be included in the study. A third clinical trial is trying to see if antiviral drugs combined with mesenchymal stem cells can improve the response to FIP treatment. The goal of the study is to determine whether cell therapy can enhance the natural antiviral immune response and promote the regeneration of lymphatic tissue after infection. The two treatment groups in this study receive either oral GS-441524 along with stem cell infusion or oral GS-441524 with placebo. Cats must be between 3 and 12 months of age and suffer from the wet form of FIP. Owners interested in enrolling their cats in these clinical trials must reside near Davis, California due to the need for repeat follow-up visits. For more information about these tests, call the Clinical Trials Office at 855-823-1390. Although we do not currently have the final results of these treatment studies, field cases that have been assigned to different treatment groups are generally doing very well.

The Center for Companion Animal Health (CCAH) at the University of California, Davis, also used donations from the SOCK FIP to support Drs. Patty Pesavento and Terza Brostof's fourth project. They lead a team of biophysicists, immunologists and vaccinologists in the development of an mRNA vaccine against feline enteric coronavirus (FECV) and its mutant biotype FIP virus (FIPV). This vaccine, based on the technology used to produce the modern mRNA vaccine for COVID-19, will hopefully lead to the generation of sufficient immunity to reduce the incidence and negative consequences of diseases such as FIP and FECV infections. Work on this vaccine has progressed rapidly and significantly over the past year. They developed the first mRNAs to be tested and the nanoparticle molecules that coat the mRNAs so that they can be safely administered. They are currently working on methods to scale up production to begin laboratory and field testing. Since the actual virus is not present in the cat's body, there is no risk that the cat will develop the disease. This makes mRNA vaccines a potential breakthrough in the fight against feline diseases that have so far been very difficult to prevent, including FIP.

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EC22-007: EIDD-2801 (Molnupiravir): determination of oral dosage and confirmation of its efficacy in cats with FIP

Original article: EC22-007: EIDD-2801 (Molnupiravir): establishing an oral dose and evidence for efficacy in cats with FIP

Feline infectious peritonitis (FIP) is a highly fatal viral disease of cats with a worldwide incidence. Several antiviral agents have recently been shown to be promising in the treatment of cats with FIP. Despite these findings, there is currently no legal FIP treatment approved by the Food and Drug Administration (FDA), so many owners turn to unlicensed antivirals purchased online. Due to the ongoing COVID-19 pandemic, several antiviral drugs have recently been approved for oral use in human patients. One of these antivirals is the nucleoside analog EIDD-2801 (molnupiravir). EIDD-2801 causes hypermutation of developing viral RNA, effectively terminating the viral replication of many different RNA viruses. This antiviral agent has been developed for oral use in human patients at home. The use of EIDD-2801 in human medicine may facilitate veterinary use. An orally administered antiviral compound would be advantageous for the treatment of cats with FIP administered to a client. We will determine the effective oral dosage of EIDD-2801 and evaluate the efficacy of this compound in the home treatment of cats owned by a client with naturally occurring effusive FIP.

(Bria Fund)

Grant ID: EC22-007
Status: Active
Year: 2022
Grant amount: $33,550
Investigator: Brian Murphy, DVM, PhD, Dip ACP; Krystle Reagan, DVM, PhD, Dip ACVIM (SAIM); University of California, Davis

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EC22-005: Acute phase proteins and micro-RNA signatures for the diagnosis and prognosis of feline infectious peritonitis.

Original article: EC22-005: Acute phase protein and micro-RNA signatures for the diagnosis and prognosis of feline infectious peritonitis.

Feline coronaviruses (FCoV) are found in the intestines of most domestic cats and usually do not cause any problems. Unfortunately, under certain circumstances, they can move into the immune cells in the blood and mutate, causing infectious feline peritonitis (FIP). Unfortunately, FIP affects 5-10 % domestic cats, especially young breeding cats and cats in rescue centers. Until recently, she was always deadly.

FIP is a mysterious and dreaded disease; in addition to the fact that its cause is not sufficiently known, it is difficult to reliably diagnose it and, until recently, it has responded poorly to all treatments. However, COVID-19 has resulted in the development of Remdesivir and its co-drug GS-441524, and these drugs appear to be remarkably effective and have, in preliminary studies, cured> 70 % cats with FIP after 12 weeks of treatment. Unambiguous diagnosis is becoming increasingly important nowadays.

Accurate diagnosis has long been a holy grail for FIP research: our goal is to i) examine the profile of certain proteins in the blood (known as acute phase or APP proteins) that increase in response to infection ii) while focusing for the first time on the potential role of micro -RNA (miRNA) signatures, which could prove successful in a new and sensitive diagnostic test.

We hope that this study will allow us to better understand FIP and diagnose it more accurately. We also hope to be able to identify which profiles suggest that the cat will respond well to treatment and which will not, thus saving it from the suffering associated with FIP and the potential inconveniences associated with treatment that will not help it.

(Bria Fund)

Grant ID: EC22-005
Status: Active
Year: 2022
Grant amount: $7,500
Investigator: Professor Danielle Gunn-Moore (DGM), BSc (Hon), BVM & S, PhD, MANZCVS, FHEA, FRSB, FRCVS, RCVS Specialist in Feline Medicine; The Royal (Dick) School of Veterinary Studies, The University of Edinburgh

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Two Vaccine Platforms to Prevent Feline Coronavirus Disease

Original article: Two Vaccine Platforms to Prevent Feline Coronavirus Disease

Principal Investigator: Hector Aguilar-Carreno

Department of Microbiology and Immunology
E-mail: ha363@cornell.edu
Sponsor: Cornell Feline Health Center Research Grants Program
Title: Two Vaccine Platforms to Prevent Feline Coronavirus Disease
Project Amount: $69,920
Project Period: July 2021 to June 2022

DESCRIPTION (provided by applicant): 

While most cats infected with Feline Coronavirus (FCoV) develop mild to inapparent diarrheal disease, a subset of them develop the devastating and deadly feline infectious peritonitis (FIP). FCoV can spread via fecal-oral or respiratory routes, particularly in cat shelter environments. Coronaviruses have three envelope glycoproteins, S, E, and M, but the surface protein (S) is in charge of viral entry. S binds the cell surface receptor and then merges the viral membrane to the cell plasma or endosomal membranes, causing viral entry. S also causes cell-cell fusion (syncytia) post-infection. The S protein of most coronaviruses is also highly immunogenic. The devastating FIP disease begs the development of protective vaccines. We identified a small molecule, XM-01, that embeds within viral membranes and inhibits membrane fusion. Importantly, this novel method of inhibition renders virions noninfectious, while maintaining the native conformations of the surface glycoproteins, ideal for eliciting effective immune responses against such viral glycoproteins. Remarkably, vaccination with XM-01-treated influenza virions yielded an increase in neutralizing antibodies and survival rate, and a decrease in morbidity and mortality upon viral challenge in a mouse model, as compared to the traditional formalin-inactivated influenza vaccine. Thus, our Aim 1 will be to determine whether XM-01 can be used to develop a FeCoV inactivated vaccine. Importantly our recent preliminary data includes already determined conditions for complete FCoV inactivation. We will optimize XM-01 inactivation of FCoV in preparation to determine whether this vaccine can yield a robust immune response against this virus. Additionally, our lab has successfully used replication-incompetent vesicular stomatitis virus (VSV)-based pseudotyped virions to vaccinate and protect hamsters against Nipah, Hendra, and Ebola virus diseases with 100% safety and 100% efficacy (manuscript in final revision for Nature Publishing Journals Vaccines). Our Aim 2 will use the replication-incompetent VSV system to develop a vaccine against FCoV. We will optimize incorporation of FCoV-S into VSV virions in preparation to determine whether this vaccine can yield a robust immune response against this virus. As both inactivated and replication-incompetent virions vaccine platforms have been successfully used to prevent other viral diseases, the completion of our Aims will allow our vaccine platforms to readily advance to vaccination clinical trials/licensing.

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