S1 EP8 FIP
The Vetrospective Podcast S01 E08: FIP
Dr. Kent speaks with Dr. Terza Brostoff about FIP –
Feline Infectious Peritonitis in this episode of The Vetrospective.
Dr. Terza Brostoff: Our success rate is really, really good. We went from 100% fatal to seeing mortality in these cats somewhere around 15 to 20%. That is a massive, massive improvement, but it’s still not 100%. We are still losing cats to this disease, and that is unacceptable.
Dr. Michael Kent: Hello, and welcome to The Vetrospective. This is your host, Dr. Michael Kent, here to give you a perspective on topics surrounding companion animals in veterinary medicine. I’m a professor of radiation oncology at the UC Davis School of Veterinary Medicine. Today’s topic is FIP, feline infectious peritonitis. It’s an infectious disease that is really unique in how it works and how deadly it is. This disease often has outbreaks in cats who are housed in groups, whether this is catteries for cat breeders or shelter population. FIP is devastating, causing rapidly progressing clinical signs that, left untreated, lead to death. It was not that long ago that there was no therapy at all, and in the beginning, the first drug, which was not approved for cats, was literally being smuggled into the country to try to save kittens and cats who were affected by FIP. The treatment and prevention of FIP is a rapidly evolving area in translational medicine. Dr. Terza Brostoff is here to speak with us today about FIP and what we are doing to stop this disease. Dr. Brostoff is an assistant professor of immunology, having joined the faculty at UC Davis around two years ago. She did her DVM and PhD at UC Davis and then went into small practice for a few years before going on to do her postdoctoral work at UC San Diego. She is a diplomate at the American College of Veterinary Microbiology with subspecialties in immunology and virology. Thank you, Dr. Brostoff, for joining me today on The Vetrospective to speak about FIP.
Dr. Terza Brostoff: Thanks for having me.
Dr. Michael Kent: Of course. So before we begin speaking about FIP, why did you get into veterinary medicine? And maybe you could talk about what caused you to have an interest in immunology and virology in particular?
Dr. Terza Brostoff: Sure, yeah. So, I was one of those little kids who, from the time I could recognize a dog for what it was, would try to pet every single dog that I saw and wanted to be a veterinarian from the time I could say it as a little kid, according to my parents. So always knew that I wanted to go into veterinary medicine, but the research side of things and the virology side of things came about a little bit later in my life. I was fortunate enough to have worked with an amazing shelter veterinarian during my undergraduate education. And it really opened my eyes to there being more than just small animal clinical practice out there. And I really started taking an interest in infectious diseases. And what about a shelter environment made those animals so much more predisposed to certain types of infections compared to normal client-owned dogs and cats? And that sort of started me on this pathway. The immunology came about a lot later. I actually really didn’t like immunology when I was studying it at first. But having chosen a career in virology and working a lot on vaccine development, immunology is a really important topic related to how vaccines work, why they work, and how they’re different than getting a natural infection. And so I’ve kind of learned it on the side. And it’s taken over my life in many ways, but it’s been a fun ride.
Dr. Michael Kent: So, when you were in vet school here at UC Davis, you were in this unique program, the Veterinary Scientist Training Program, or what we call the VSTP. So, it’s a combined DVM and PhD program. So why did you join this program and how did it prepare you for your career?
Dr. Terza Brostoff: So, I actually, the summer before I started veterinary school, started, I decided that I was interested in research and I started looking up different faculties’ research interests. And I reached out to a handful of the faculty here that were working on projects I found interesting. And one of those faculty happened to be one of our amazing anatomic pathologists, Patty Pesavento. And at the time, she was working exactly on what I was interested in, on viruses that affect cats in shelters. So, I reached out to her and I said, “I have nothing planned for this summer before vet school. Is there any way I could come poke around the lab”? And she graciously allowed me to work with her that summer and I absolutely fell in love with the work she was doing and with her as a mentor and everything else is his history.
Dr. Michael Kent: I always like learning about people’s paths and where they wind up because they’re often really varied. And I know after you finished veterinary school and after you finished your PhD, you went into private clinical practice for a few years.
Dr. Terza Brostoff: I sure did.
Dr. Michael Kent: So, what brought you back to research and what did you learn in private practice that shaped your future career?
Dr. Terza Brostoff: So, I always knew, again, I was that little kid that wanted to be a veterinarian. And doing the dual degree program, it really gave me an idea of how important research is and how it shapes everything that we do in the clinic. After finishing that dual degree program here, I decided pretty early on that I wanted to spend some time in practice. I didn’t know what that was going to look like, if it was going to mean that I did a residency, an internship, or if I just went straight into clinical practice. And leading up to my senior year, I loved clinics. I loved interacting with clients. I loved the patient care. And so I decided that I wanted to spend, I decided at that time five years exactly five years in clinical practice before I came back to academia. And three years in, COVID hit, and I decided three years was gonna be just enough. And so, I returned and did that postdoc in early mid 2020, but knew that was something I wanted to use to shape my academic career as well. I think those years in practice were invaluable. I had incredible mentorship at the practice that I was at, and I really got a good feel for what it means to be an on-the-ground veterinarian, how to communicate that to them, what is important for them, and really understanding what clinical research can do and how it can benefit the majority of our patients.
Dr. Michael Kent: So really it kind of cemented what you wanted to do in some ways, and then you’re able to step back into a more academic kind of program.
Dr. Terza Brostoff: 100%, yeah. It’s actually kind of similar to the concept of the way that we structure our dual degree program here, where you start with your first two years of basic science, and then you do the PhD, and you use what you learn in those first two years for your PhD, and then you learn what you use, what you learned during your PhD back again in the clinical years. So, it’s kind of of the same idea, only taking it a couple steps further, I guess.
Dr. Michael Kent: Now I know your interests go beyond FIP, but I really wanted to talk to you about FIP today. Can you describe to me the feline coronavirus and how this relates to FIP, the disease entity we call feline infectious peritonitis?
Dr. Terza Brostoff: Yeah, absolutely. So ,cats, there’s a virus called feline coronavirus, and it’s actually a really, really common virus in cats. It is not very closely related to SARS-CoV-2. It’s in a different subfamily, but it causes a really, really unique disease in a very small subset of those cats infected with feline coronavirus. So typically, cats will get infected with the normal coronavirus, pretty young, in their lifetimes. It may or may not cause a little bit of diarrhea, but most cats clear the infection without having much of a problem.
Dr. Michael Kent: So, an owner might not even notice that their cat was exposed to this coronavirus.
Dr. Terza Brostoff: Exactly. And a lot of cats are exposed to it at a young age, and we never know. We don’t test for it. It’s not usually clinically important in those cats.
Dr. Michael Kent: And what about the virus itself, how does it change or why does it cause critical disease in some of those cats?
Dr. Terza Brostoff: We don’t have a really good understanding of exactly which cats are going to go on to develop FIP, because as I mentioned, a lot of them do get the virus pretty early in life. But the accepted theory at this point is that in a very small subset of cats, for whatever reason, the virus will actually undergo some mutations that cause it to leave its normal area where it hangs out in the cat, which is the GI tract, and it can actually spread everywhere throughout the body. And when that happens, the cat develops FIP, or feline infectious peritonitis. FIP with the virus literally anywhere in the cat’s body causes really, really severe disease. And again, untreated is considered nearly ubiquitously fatal or 100% fatal.
Dr. Michael Kent: Yeah. So, if we have 1000 cats, do we know probably how many were exposed to feline coronavirus in their life?
Dr. Terza Brostoff: It depends a lot on what the cat did when it was growing up. So, cats that have spent a lot of time in a highly dense environment, as you mentioned earlier, cats that are coming out of breeder environments or from shelters, those cats that have a lot of access to other cats and other cats’ litter boxes tend to be more likely to be infected. And some of the estimates range in the high 80s to even 100% of cats in those environments. are frequently found to have been infected with the virus. Of course, we don’t know quite as much from our community cats because we don’t test them, but it’s likely that those cats have a much lower prevalence of coronavirus if they are outdoor cats that grew up outside and spend their whole lives outside because they’re not coming into quite as much contact with other cats and with other cats’ poop.
Dr. Michael Kent: Fair enough. And so if we have, 1000 cats have been exposed to the feline coronavirus, you said a very small percentage. Do we have an idea of how many are going to have, at least current theory, that they have the mutations that happen that make this a more virulent virus, a more aggressive virus that’s going to cause this disease entity?
Dr. Terza Brostoff: And again, it depends on a lot of things as well. There have been studies that have published as low as 0.5% of those cats, and then some say in certain environments, up to 10%. We know that genetically related cats, if one of the cats in a litter gets FIP, it is more likely that other cats from that particular litter are going to go on to develop it. That’s likely where those higher percentages come from, is groups of cats that are highly genetically related. But in general, most of our estimates at the low end are around 0.5 and up to about 2%. That’s considered typical.
Dr. Michael Kent: So, there’s some predispositions some cats or kittens have to developing this in some ways. So, it must be a body host virus interaction to some degree.
Dr. Terza Brostoff: Yeah, absolutely. There’s likely contribution from the cat’s genetics and likely the cat’s immune system plays a role as well. There’s also likely some contribution from that actual initial virus that’s infecting the cat. And we know there’s different types of viruses that seem to behave a little bit differently in different cats. So, all of those.
Dr. Michael Kent: Different strains of the feline coronavirus.
Dr. Terza Brostoff: Yeah.
Dr. Michael Kent: Just to put in a little more understandable terms for me. So, I know there’s different clinical forms of this. The 2 main forms, at least that I’ve heard broken down are the dry form of FIP and the wet form. Can you kind of describe those clinical scenarios that we see in kitties and kittens and cats?
Dr. Terza Brostoff: Yeah, so when cats first get FIP across the board, whether they have the dry form or the wet form, the first thing owners typically see is just a cat that generically doesn’t feel good. So, these kitties have low energy, low appetite, they might not be playing, they’re usually young, so they might not be playing with their litter mates as much, they might be hiding more. The wet form is the most common form that we see clinically, and it happens when fluid starts to build up in any one of the kitty’s body cavities. So it can happen in the belly, it can happen in the chest, it can actually happen in the heart sac as well. And it can be any combination of those cavities that fluid can build up in. That’s by far and away the most common form we see. And sometimes owners will notice it looks like their kitten is getting rounder and having a big, big belly.
Dr. Michael Kent: So, something that most people say, they need to be dewormed and maybe they just have general malaise or flu-like symptoms or clinical signs that are non-specific and then they become pretty ill.
Dr. Terza Brostoff: Yeah, exactly. And they can. They do absolutely look like a kitten that needs to be dewormed. But if left long enough, it will definitely get a lot worse than what we see with worm bellies. And again, in a kitten that feels really, really sick.
Dr. Michael Kent: And then what’s the disease course if we can’t intervene?
Dr. Terza Brostoff: So the disease course, whether they have the wet form or the dry form, and again, dry form, those cats typically act very similar to the wet form cats. They just act like they’re not feeling well. Sometimes we’ll see some involvement in the eyes or in the nervous system. They’ll get wobbly and have a harder time walking, potentially having seizures as well. But regardless of the form, they will go on to feel more and more ill, stop eating, stop drinking. And again, without antiviral therapy, without intervention, most people agree it’s nearly, if not 100% fatal in these cats.
Dr. Michael Kent: 100% fatal is pretty serious.
Dr. Terza Brostoff: It is, yes.
Dr. Michael Kent: So just a few years ago, this was considered untreatable. Do supportive care, but pretty much like you said, 100% of these cats died. And that was even with the best supportive care we could give them. So, what changed this? What happened?
Dr. Terza Brostoff: So, we’re, it’s fortuitous that we’re here at UC Davis. We played a big part in this story as it’s unfurled in curing FIP. So ,one of our faculty, one of our emeritus faculty, Niels Pedersen, helped discover one of the antivirals that we use today to treat FIP. It’s got a really a name that just rolls off the tongue. It’s called GS441524. That drug is actually really closely related to one of the major antivirals that was used in the COVID-19 pandemic or remdesivir. So, they’re metabolites of each other. So very, very closely related and likely that Dr. Pedersen played a role in our ability to use that drug during the pandemic as well.
Dr. Michael Kent: And I know he’d I’ve been studying this for years. So why did it take us so long to come up with a treatment? Did we just not have the drugs? Did we just not think about it? I know this has been a disease that for decades we’ve really fought hard and lost.
Dr. Terza Brostoff: Yeah. So it did take a very long time for him to discover it and there were problems with licensing its use in the United States. And because we knew how effective it was, a black market popped up very quickly developing this, getting access to this drug, primarily from some pharmaceutical companies in China. And so for many, many years, people were buying this drug on the black market because it was literally the only thing available that could actually save these cats. And that market to this day has been very, very successful and has saved a lot of cats’ lives.
Dr. Michael Kent: Yeah. So how does, I’ve got this right, GS441524 work? Like what is the antiviral doing? Is it killing the cells that are virally infected? Is it stopping the virus? How does it work in general?
Dr. Terza Brostoff: Yeah, so it’s called a nucleoside analog, and it prevents the virus from being able to replicate. So, the virus has an enzyme that it encodes for, and that enzyme is meant to make more virus. So it makes the virus genome unable to reproduce. And when this drug, this drug fakes the virus out. It makes the virus think that it’s one of the building blocks that it should use to make more virus, when in fact, when it uses that particular building block, the one that comes from the drug, it actually stops the virus from being able to do anything more with its own genome. So it stops the virus from being able to make more virus inside the cell.
Dr. Michael Kent: And you said it’s been pretty effective, but what cases does it not work in? It’s not 100% effective, is it?
Dr. Terza Brostoff: No, it’s not. Most of the studies that we have at this point, because we actually have years of data, and this drug was actually being used pretty extensively in other parts of the world before we started using it as much as we have here in the United States. So, there are a good handful of papers that were published before we had it available here legally. And most of these papers show that efficacy is around 80 to 85%, depending on the study that you read. Most of the time, if kitties don’t respond to the drug, it happens within the first few days to a week or so. And the prevailing theory, although we don’t have enough data on this yet, is that we just caught those cats too late. So FIP is really, really difficult to diagnose, and especially in those dry form cats, where we don’t have fluid building up in one of their body cavities, it can look like a lot of different diseases, and we don’t have one very, very good, easy-to-do diagnostic on a live cat that gives us good certainty that cat has FIP. So that 80% is, for the most part, kitties that we likely didn’t get to in time, and they were too systemically compromised to make it long-term. We do see a small percentage of cats who relapse, and we’re still in the process of defining what exactly relapse means, because it’s really, really hard to prove that it was that same first coronavirus that infected a cat, causing its FIP and then coming back, or never being eliminated by the antivirals. But there are a percentage of cats that do relapse when they come off of drug. And that contributes to that 80 to 85% as well.
Dr. Michael Kent: So, what other tools does a clinician have in their toolbox? If I’m just going to call it GS, it’s easier. If GS fails and we suspect that FIP either wasn’t cleared or is coming back, what else can we do? What else do we have out there?
Dr. Terza Brostoff: So, there’s a lot of research and lots One of it has come out of UC Davis, along with Dr. Krystal Reagan and now our new internal medicine specialist, Erin Lashnitz.
Dr. Michael Kent: Who we talked about fleas with already.
Dr. Terza Brostoff: Yeah, so we have a big FIP community and we are, this is a huge part of FIP research now, is looking into beyond GS, what other drugs we can use to treat this disease. So ,there are other nucleoside analogs that we can use.
Dr. Michael Kent: Other antivirals.
Dr. Terza Brostoff: Yes, other antivirals. Antivirals of the same class, and some… some of different classes as well. So. there are trials looking at, again, specifically remdesivir. There’s been a lot of work done on molnupiravir and some of molnupiravir’s related compounds. And we also have a trial right now looking at Paxlovid to treat these cats.
Dr. Michael Kent: So, these are many of the same drugs that are used to treat viral infections in humans or even in COVID more recently with the pandemic.
Dr. Terza Brostoff: Yeah, absolutely.
Dr. Michael Kent: So, I know there’s been an FIP vaccine that’s literally been out for several decades. So why has this vaccine failed to protect cats from developing FIP at this point? How do you know that?
Dr. Terza Brostoff: There is one USDA-approved vaccine for use to treat or to prevent FIP in cats. It was developed in the 1980s. So, this virus has been around for a while. It was first described in the 60s and we had a vaccine in the 80s. There are a couple of reasons why in general this vaccine is not recommended for use in cats. It is, so we didn’t talk about the two types of, we talked about the types of FIP, the wet form and the dry form, but the virus itself, there’s actually two different genotypes. So, two different viruses that look very different on that outer spike protein. So, spike has become very famous because it’s the target of the COVID-19 vaccine. And we have two types of feline coronavirus, type 1 and type 2. And the big difference between the two is that spike protein.
Dr. Michael Kent: So, a spike protein is just something that sits on the surface. And what does the spike do?
Dr. Terza Brostoff: Yeah, so the spike is one of the most important proteins on the virus for its structure and for getting into cells. So that spike has what we call the receptor binding domain on it. That’s the portion of the virus that it uses to attach and enter into the cells that it’s going to infect. So, it’s a really good target for a vaccine in theory, because if you can get an immune response to that part that the virus needs to get into a cell, and if you can block that, you can block the virus from getting into any further cells. So, it’s a really common target that we would use in vaccines normally.
Dr. Michael Kent: no, I kind of got you off topic a little bit, right?
Dr. Terza Brostoff: Sorry, I could talk about FIP all day long.
Dr. Michael Kent: Oh, that’s good, because I may just hold you to that. No. So we were talking, oh gosh, what were we talking about? We were talking about how the original vaccine from the 80s, why it’s not recommended now.
Dr. Terza Brostoff: Yeah, so there’s the type 1 and type 2 spike. And type 1 is by far most common in the world. We see type 2 infections pop up sporadically, but they are less than 20% of the infections that happen in most cats. The theory behind that vaccine is getting a good immune response to that spike protein, and unfortunately, that vaccine is a type 2 spike. So we don’t get protection from both, out of spike alone.
Dr. Michael Kent: It doesn’t cross-react.
Dr. Terza Brostoff: Exactly, yeah. So, a cat that’s immune to type 2 can still get infected with type 1 and vice versa. So, this vaccine is against the type that is less common in circulation in cats. It’s one of the big problems with that vaccine. The other big problem is that the feline coronavirus, or FIP, is a little bit unique in that antibodies, which are one of the body’s primary ways of preventing infections, typically help if you have a good antibody response to a vaccine, that’s going to protect you from the virus, from disease. In feline coronavirus, in FIP, we know there are certain types of antibodies primarily to that spike protein that can actually paradoxically make disease worse. And so we have to be really careful when our major target for a vaccine is that spike protein that we don’t actually end up causing the animal to develop antibodies that are going to make disease worse.
Dr. Michael Kent: Maybe make the virus get into the cell better, or do we know why that happens?
Dr. Terza Brostoff: Yeah, so it’s a little bit complicated. So, antibodies normally bind to the outside. So ,antibodies to spike would bind to the outside of the virus because spike is on the outside surface of the virus. The enteric form or the GI form, that normal feline coronavirus that most kittens get, the target for the virus is cells in the GI tract. We know that with the mutated FIP form, the virus actually starts infecting instead of just cells in the GI tract, it preferentially starts infecting some of the white blood cells in the body. They’re called monocytes and macrophages. Those cells actually have receptors for antibodies. And so a virus that is bound to antibodies can actually get into its new target, those monocytes and macrophages, those white blood cells, easier. So, we see higher mortality and faster mortality in those cats that are showing this antibody enhancement of infection.
Dr. Michael Kent: So those cells, which are just doing surveillance, actually wind up, in a sense, getting enhanced infection because of it.
Dr. Terza Brostoff: Yeah, and the virus can get around the body easier, faster, and more efficiently if it can get into those cells better.
Dr. Michael Kent: And I know you said that the coronavirus that infected humans and created the SARS COVID-19 pandemic or COVID as we know it, is a different subclass of virus than the coronavirus in cats. And I know the coronavirus in cats, as you were talking about, is at least largely GI and not respiratory to the start. So, what have we learned from the human pandemic that we can bring back to cats?
Dr. Terza Brostoff: Yeah, so we’ve learned a handful of things, and I think those of us in the FIP world are all across the board grateful that COVID-19 looks nothing like FIP in cats, because it’s a very,
Dr. Michael Kent: very… Yes, when I heard it was first a coronavirus, I went, Oh God, I hope it’s not this 100% fatal disease that we’re seeing in cats.
Dr. Terza Brostoff: Yeah, and I think as well, a lot of us who are really entrenched in the FIP world, we were really worried when all of the vaccine strategies for COVID-19 were, for the most part, targeting that spike protein.
Dr. Michael Kent: Targeted spike wasn’t going to make disease worse.
Dr. Terza Brostoff: Yeah, exactly. And it does not seem to be the case. Thank goodness.
Dr. Michael Kent: Thank goodness, yes, because I know I’ve had six or seven shots now for COVID.
Dr. Terza Brostoff: I think most of us have at this point. And thank goodness that vaccine was very safe, very effective. And we do not see this antibody enhancement of infection. I think we’ve done a worldwide epidemiologic study at this point. We can confidently say that is not a player. We don’t see vaccinated people getting worse disease for sure.
Dr. Michael Kent: No, in fact, it’s the opposite, right?
Dr. Terza Brostoff: It absolutely is, yeah. But I think, you know, no one really expected mRNA vaccines to take off, in in the world in general as far as vaccine platforms go. And I think this was the first widespread big use of that type of vaccine, which had been developed for years and years and years before the pandemic, primarily actually in your field of specialty, looking at its use in cancer vaccines.
Dr. Michael Kent: In a treatment vaccine, but not a preventative vaccine.
Dr. Terza Brostoff: Exactly, exactly, yeah. So, I think that was the other big thing that we’ve learned is that there’s a new potential platform that we can use that seems seems to be really effective and quite safe.
Dr. Michael Kent: So I know you’ve been working, we have a pretty large FIP group here that’s really transdisciplinary. You know, everyone from our basic or fundamental scientists and those who are translational scientists to those clinicians on the front line who treat these cases. And the unique idea of quote unquote bracketing the cat, I think maybe Dr. Pesavento, who you mentioned earlier first, I’ll have to get her on this show. First coined it, but could you explain what we mean by the term bracketing the cat?
Dr. Terza Brostoff: Yeah, we do. We have a lot of researchers working on a lot of different aspects of FIP here at UC Davis. So, lots and lots of research going into the basic science, just understanding better how this virus gets in and causes the disease it does. But looking at it from the front end of the cat, so vaccine development and prevention all the way through to the back end. So treating it and developing better antivirals, publishing more data so that we know how best to use these antivirals, what doses, what drugs, how long to use them for, et cetera. That’s what we mean by bracketing the cat, encompassing this disease from nose to tail.
Dr. Michael Kent: And understanding the whole mechanisms, how it works, and some of this is still a mystery.
Dr. Terza Brostoff: Oh, a lot of it is still a mystery.
Dr. Michael Kent: So, we have drugs like GS that we talked about and others like Paxlovid or remdesivir. And there’s other antivirals I know that you mentioned as well. Why do we need a vaccine? We can just treat. What’s the unmet need? Why should we have a treatment? Sorry, a preventative vaccine.
Dr. Terza Brostoff: Yeah, there’s a handful of downsides to having to treat a disease after it’s already developed. As I mentioned before, our success rate is really, really good. We went from 100% fatal to seeing mortality in these cats, somewhere around 15 to 20%. That is a massive, massive improvement, but it’s still not 100%. We are still losing cats to this disease, and that is unacceptable. Additionally, again, we don’t really know what the perfect drug for any particular cat is or how long we’re going to have to treat any particular cat for. But at the present time, treatment still remains quite expensive. It’s on the order of a couple thousand for a full course of treatment as we tend to prescribe it today.
Dr. Michael Kent: We were talking about shelter cats, breeders. This would be too expensive for shelters to bear the cost of this and for many breeders too.
Dr. Terza Brostoff: And for most pet owners. Most pet owners can’t afford to treat their new cat that they just brought into the household that they expect to be at least mostly healthy for at least the next 10 years. And then right off the bat, they have a cat that requires hundreds, if not thousands of dollars of diagnostic tests and hospitalization, and then a couple thousand just to treat the cat.
Dr. Michael Kent: These drugs are human drugs, so they’re quite expensive and still mostly on patent, right?
Dr. Terza Brostoff: Yeah. Yep. That’s one of the problems for sure. The other problem, of course, being that mortality rate, that no matter what we do, even if even with all the money in the world, some of these cats still can’t be saved.
Dr. Michael Kent: So I know you’ve been working very closely with others at developing a vaccine. So why could this one work when the previous tries at making an effective FIP vaccine have failed? How are you thinking about this? How are you thinking out of the box?
Dr. Terza Brostoff: Yeah, so we are using a totally different strategy than what’s been tried for cats in FIP before. We’re actually targeting a different protein. So, I mentioned that spike protein on the surface is the one that’s potentially problematic when it comes to vaccinating cats and making disease worse, we’re actually targeting one of the proteins that’s present only on the inside surface of the virus. So, while the cat may develop antibodies to that protein, those antibodies won’t stick to the outer surface of the virus, and they won’t help the virus get into its white blood cell target that it likes to get into. So we’re doing that, and in addition, we’re using the mRNA vaccine platform, which to date has not been published on in cats.
Dr. Michael Kent: So, can it still find the target if it’s hidden on the inside of the cell?
Dr. Terza Brostoff: Yeah, so it seems like a kind of kooky strategy if all I’ve talked about is antibodies preventing infection. And I’m saying antibodies aren’t going to hurt the cat, but they’re not necessarily going to do anything to help these cats survive and protect them from FIP. So, there’s two arms of the immune system. There’s our antibody arm, that humoral arm and there’s actually the other entire other half that we don’t tend to talk about as much because it’s harder to study. But there’s half of the immune system ish is dedicated to a particular cell type, a white blood cell that can actually recognize and kill cells that have already been infected. And so.
Dr. Michael Kent: Natural killer cell?
Dr. Terza Brostoff: Nope.
Dr. Michael Kent: Nope, not that one.
Dr. Terza Brostoff: That would be too logical.
Dr. Michael Kent: That would be too logical. And that’s part of the innate system, but what cell are you talking about?
Dr. Terza Brostoff: Yeah, so the cell type I’m talking about, they’re called cytotoxic, so cytocell toxic killing, cytotoxic T cells. So, we have B cells that make antibodies, and we have T cells. And one of the types of T cells, and the one that we’re really banking on for this vaccine helping with, are called cytotoxic T cells. Our theory is that we are going to get really, really good immune community via the cytotoxic T cells. And they’re going to recognize infected cells either after the cat’s already been infected before the vaccine or afterwards and wipe out that reservoir before the feline coronavirus has a chance to mutate to that FIP form.
Dr. Michael Kent: So how far along are you? the $1,000,000 question
Dr. Terza Brostoff: The $1,000,000 question
Dr. Michael Kent: And hopefully not going to cost $1,000,000. I know this is it’s hard.
Dr. Terza Brostoff: It absolutely is hard, and that is something that we are very conscious of. We are at a point where we have a vaccine in hand, and we’ve done some preliminary tests in cats. And at this point, we’re trying to see if we can get an industry partner to start moving this vaccine forward.
Dr. Michael Kent: That’s really exciting. So, what do you say to someone now who’s just adopted a kitten and who becomes ill with FIP or caring for their cat who has FIP? Putting your clinician hat back on and your scientist hat back on, what would you say? What would you say to someone?
Dr. Terza Brostoff: About the vaccine or just in general?
Dr. Michael Kent: Just in general, vaccine and treatment and because this has been such a devastating disease for cat owners for so long.
Dr. Terza Brostoff: It is remarkable to be able to look an owner in the eye and tell them that we can actually save their cats. We’ve had so many clinical trials here at Davis and so, so many grateful owners. I had one in particular. She is a veterinary technician who’s been in the field for many years and her own cat developed FIP and was enrolled in one of our clinical trials. And she cried at every single appointment because when her cat first got the diagnosis, she was devastated. And that devastation and then realizing that this is something we can actually treat now was overwhelming for her. So, it’s so powerful to be able to literally save lives because we do a lot of medicine during the day and it’s rare that we actually save a life, not to mention the life of a young kitten, you know, who…
Dr. Michael Kent: Who’s so sick
Dr. Terza Brostoff: Who’s so sick and who has a whole lifetime ahead of them.
Dr. Michael Kent: Yeah, that’s very cool. And now I know a lot of people have heard of FIP, but more people are more familiar with some of the other viruses like FeLV or FIV. How different is FIP from these diseases?
Dr. Terza Brostoff: FIP is its own beast. It is, this is the only coronavirus we know of in cats. And it’s really, really different than things like retroviruses, some of those other viruses we think of more commonly. And the disease itself is absolutely a one-off. We tend to think of either, these retroviruses and these chronic persistent diseases, things like feline herpes that the cat lives with its whole life, versus other acute viral infections, things like feline calicivirus or feline panleukopenia virus, where they get sick acutely over a short period of time. And if they survive that infection, they’re usually, it’s a one and done. FIP is really different. These cats are kind of, yeah, they’re kind of sick for a period of time. They get the virus, they, and then weeks to months later, they break with a really, really severe disease, potentially even years later with a really severe disease. And it’s definitely unique as far as viruses go, unique in a bad way.
Dr. Michael Kent: So, I’m gonna wrap us up by asking what more do we need to learn about FIP? What key pieces of information do you want to know so that we can bracket the cat?
Dr. Terza Brostoff: This is so this is the this is the Dr. Brostoff question and not what the field wants to know. The field is definitely moving towards we need better diagnostics.
Dr. Michael Kent: We need a test. We need blood tests. We need something.
Dr. Terza Brostoff: Something simple, something we can do non-invasively, something we can do quickly.
Dr. Michael Kent: With the snap test we have for FeLV and FIV, which we don’t have for FIP.
Dr. Terza Brostoff: Exactly. The problem is that these cats are all infected with feline coronavirus. So just finding that virus there doesn’t tell us that the cat has FIP. My $1,000,000 question, the avenue I am most interested in is what immune responses are actually protective in these cats? Because we know so many cats go on to clear their infection or never develop FIP. That’s the vast majority of cats. But what is it about the immune response that is allowing some of these cats to get so sick, because we know a lot of the disease that we see from FIP is actually the cat’s immune response to the virus.
Dr. Michael Kent: So it’s basically saying, oh my God, I’m infected. And then the response from the cat is so strong. that it can actually kill the cat.
Dr. Terza Brostoff: Yeah, exactly. So that’s where my research is headed, is figuring out what type of immune response is going to be protective and why most cats do fine. What are they doing differently in terms of immune response than cats that succumb to FIP?
Dr. Michael Kent: This has been really great. I appreciate you taking the time today to speak with me and The Vetrospective listeners. So please keep up the good work.
Dr. Terza Brostoff: Thanks so much. I had a great time too.
Dr. Michael Kent: Thanks.
The Vetrospective, as with life, takes a village. I want to thank those who suggested I start this project and everyone who has encouraged and supported me along the way. Particularly, I want to thank our producer and director, Danae Blythe-Unti, Nancy Bay, who is our program coordinator, our sound mixer, Andy Cowett, and theme music was composed and produced by Tim Gahagan. Thank you all, and we’ll see you next time.
