Revolutionizing Canine Health: The Promise of Monoclonal Antibodies Against Parvovirus

Discover the lifesaving potential of monoclonal antibodies in the fight against canine parvovirus as Laurie Larson shares insights on this innovative treatment. We unravel the complexities of parvovirus and how traditional vaccines sometimes fall short due to maternal antibodies. Laurie takes us through the riveting findings of a pivotal study published in JAVMA, revealing the success of monoclonal antibodies in significantly boosting survival rates in dogs. This episode is a beacon of hope, shedding light on the urgent need for prompt intervention at the first sign of infection. For veterinarians seeking to navigate client communication about this groundbreaking treatment, our conversation offers indispensable advice. Together, we're rewriting the narrative on combating canine parvovirus.

Full article: https://doi.org/10.2460/javma.23.09.0541

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Transcript

Speaker 1: 0:01

You're listening to Veterinary Vertex, a podcast of the APMA journals. In this episode we chat about the early administration of canine parbovirus monoclonal antibody with our guest, lori Larson.

Speaker 2: 0:20

Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today, we have Lori Larson joining us. Lori, thank you so much for being here with us today.

Speaker 3: 0:32

I'm so excited to be here. Thank you for the invitation.

Speaker 1: 0:37

Of course, let's dive right in. As a clinician, I know that parovirus can be deadly for unvaccinated dogs and, unfortunately, I've seen all too well how it can take a huge emotional and financial toll on pet owners. Your JAVMA article discusses a new treatment strategy for this disease using monoclonal antibodies. Please share with our listeners the background on this study.

Speaker 3: 0:59

Thank you. I just want to point out that it's not just unvaccinated dogs that have problems with parbovirus. I'm sure your listeners know this. But sometimes our clients feel that they did everything right. They fully vaccinated their puppy and still got parbovirus, even though that's because of when maternal antibodies are high. I just want to be sure that that's put out there that it's bugs that are susceptible to parbo. It seems that parbo will always be with us because of that maternal antibody blockage of vaccine from immunizing. But I'm very excited about this study.

Speaker 3: 1:44

As you and your listeners know, parbovirus treatment up until now has been pretty much limited to just supportive care Fluids, antibiotics, trying to keep the animal together while their immune system fights off this virus. There's really been a very strong need for a targeted approach for this particular disease and this virus. We know from multiple challenge of immunity studies and have been done to do the vaccine efficacy trials that parbovirus is highly susceptible to antibody neutralization. We call that sterilizing immunity and it's the amount of antibody that can actually prevent the virus from infecting. The virus is sterilized. We've in the past have done where we will give immune plasma or immune serum as an adjunct treatment to the standard of care. There have been a few clinical trials that have found mixed results with that approach. That's cemented for us the need for standardized antibody, a product that we would know that the dose could reliably give us certain tighter and have a good bioavailability.

Speaker 3: 3:07

This product, it's a monoclonal antibody that's built on a K9, immunoglobulin type G backbone. Then there's a high affinity mouse derived antigen binding site on this construct. It's very high affinity for the parbovirus Because it comes from the dog. The rest of that, it's very well tolerated by the dog. Our pilot studies showed that this product gave us very high titers very quickly. It came on board very rapidly within hours of IV administration. That was very promising for us. We chose to go forward with trying to get a USDA product licensure. This study in the paper in your journal presents the results from that pivotal trial.

Speaker 1: 4:08

Yeah, it's really exciting just any kind of new treatment that we can try for these cases because, like you said, it's so hard to then just supportive care and you really don't know sometimes what the end result is going to be. Yeah, so you touched on this a little bit already, but what were some of the important findings from the study?

Speaker 3: 4:27

So let's start off by letting you know that this was what we call a pivotal study. So that means that it needed to meet all of the requirements that the USDA imposes, and that's way more than we could get into in a 30 minute podcast. But we had a control group. All of the key personnel were masked to the different groups. Whether a puppy was treated or control group, nobody knew that until it was revealed. At the end we had 28 pups that were challenged with highly virulent parvo virus and then observed observed for 14 days. These puppies were eight weeks old. They all became snap positive four days after challenge, just like clockwork, and at that time they were given a single dose of either the monoclonal antibody product or saline. So, like I said, veterinarians were masked. There was one person who was dispensing who knew what they were handing, the person who was administrating the treatment After that, while during that 14 day period of observation, no further treatments were given, and that was due to the USDA requirement.

Speaker 3: 5:49

We wanted to be able to pinpoint how this product worked on its own without any other supportive care. So this was really putting it to the test. So we had 28 total dogs. Seven of them were in the control group, the ones that received saline. Of those seven dogs, they all became seriously ill with parvo virus and 57% of them met humane endpoint around days seven to eight after challenge. On the other hand, and in contrast, all 21 of our treated dogs survived this challenge and had much less severe disease signs. These results are just really encouraging. But I do need to say that this drug is not a miracle. It's not a miracle drug and it's real important that we point out that this was given at day four, so when they first went, snap positive treatment was begun immediately.

Speaker 2: 6:56

Lori, I think that's the best description of monoclonal antibodies I've ever heard. They're obviously all the rage and really I think they're revolutionizing human and veterinary medicine. So thank you for that, for myself and for listeners.

Speaker 3: 7:12

You're welcome. I teach immunology here at the veterinary school. Well, you're clearly a good teacher.

Speaker 2: 7:19

What sparked your research interest in monoclonal antibodies?

Speaker 3: 7:23

You know I've been working on fighting parvo and canine antibody for it seems like half my lifetime.

Speaker 3: 7:33

I'm one of those people who wanted to be a veterinarian since I was really young you could almost say I was born a pre-vet student, so I was already on the path to become a veterinarian, but when I was in high school now I'm aging myself but high school was when parvo broke out into the world and that had a very huge effect on me, as you can imagine, as a young, hopeful, soon-to-be someday veterinarian, and that kind of cemented for me that not just veterinary path but infectious disease and infectious disease prevention has from early time high school been a main interest of mine, and so, yeah, I think it's been 32 years that I've been working now in veterinary vaccinology and working with canine antibody in general, and I have to say that the development of this product is one of the things you know.

Speaker 3: 8:36

Being a part of that is one of the things that I am the most proud of over that entire 32-year career. I feel that this product has great potential to positively impact countless lives, and I mean not just the dogs but the people who love them too, and I'm just so honored to have been a part of it.

Speaker 2: 8:59

That's a great inspirational story, also to follow your passion.

Speaker 3: 9:03

It is definitely a passion.

Speaker 2: 9:07

As you said, it's a pivotal trial, very difficult to do, a lot of time and people and money and animals, and we're very, very honored and privileged that you decided to share it with us at JAVMA. Why did you decide to submit this manuscript to JAVMA?

Speaker 3: 9:25

Well, honestly, javma was the first one on my mind and the target for me all along, and my reasoning is that JAVMA is a journal that's accessible to clinicians. Right, there are lots of really fabulous scientific journals out there, but JAVMA seems to be the one that the clinicians read. So that's one reason. The other thing is that all of my previous experiences with JAVMA have been very positive. I really enjoy well, if you can enjoy the peer review process. For me, it feels like your reviewers really care about getting the articles as good as they can be, and I really appreciate the time and effort that the peer reviewers put in to all of the different manuscripts that I have submitted to JAVMA in the past. So, yeah, and the open access is also very good. I'm happy that anybody can see this article.

Speaker 2: 10:33

Yeah, we are too. It's very, very important. We try to take very good care of our reviewers. They're volunteers. It's a stewardship to our profession. So we offer as you probably know, we offer CE credits and all kinds of customer service-friendly things to try and get that process as smooth as possible. That's nice, Lauren. We talked about this being a pivotal clinical trial. Is this revolutionary monoclonal antibody available to clinicians today and, if so, where?

Speaker 3: 11:07

Yes, it is available. Now it's. This is an Elanco product. I'm not sure who's distributing. I'm sorry that's not my field, but yes, it is available and I'm hearing really good reports from the field.

Speaker 2: 11:26

Excellent. We're looking forward to the follow-up manuscript Five years in, maybe three years. Lauren, you shared a lot of the super important findings to your manuscript, but there's always something in every study that is a surprise. What was the most surprising finding in this article?

Speaker 3: 11:47

Well, lisa, you know I work with vaccine responses right in dogs and I'm used to seeing antibodies rise. But I was really I was surprised by the speed of the onset, of being able to detect these high titers after administration of this product. So that's a long way of saying my gosh. The bioavailability is amazing here. It seems like within hours of intravenous administration we've got it going and on board. And you know I was expecting to see good titers, but I thought it would take a couple of days to operate in the system, but wow, this came on fast.

Speaker 2: 12:35

Why do you think that is Laurie? Do you think that's part of the virus itself, or is that some serendipitous design in the monoclonal antibody?

Speaker 3: 12:43

I think it's the monoclonal, but you know that I'm not certain. I think when we have active responses by the dog, the machinery has to all engage right, to use colloquial terms, Whereas here we're giving it boom and all at once in that one single dose. And it's just very amazing to me how quickly we get very nice high titers, multiple dilutions, above what we call our sterilizing immunity threshold. And that's really important during that phase where we have viremia going on right. That's where we can try to stop that virus from continuing to spread and infect more susceptible cells, especially early on when we're trying to protect the lymphocytes right. And that seems to be what's going on with this product and how it's working.

Speaker 1: 13:47

Sounds like this could really be a game changer. So again, just thank you for sharing findings with us.

Speaker 3: 13:51

Yes, Game changer is the words that I hear over and over, and not just for me, but across the board. I hear game changer all the time and it's true. If it really is Not a miracle, it's not a miracle, but a game changer for sure.

Speaker 1: 14:08

Definitely. These cases can just be so devastating. So I think anything that can give our clinicians and our pet owners some hope is definitely something worth investigating. And for those of you just joining us, we're discussing canine parbovirus monoclonal antibodies with our guest, Laurie Larson. Laurie, how did your advanced training prepare you to write this? Manuscripts.

Speaker 3: 14:30

Well, I do have to say that my training I wish I'd spent more attention to statistics, so that's one place where I really needed help in writing this and I'm very thankful to my co-authors who helped me with that. But, as I mentioned earlier, the 32 years of working with canine parbovirus and vaccinal responses and basically prevention of parbo, I think has made me ready to write this paper and very passionate about this subject. I really want to save puppies. That's really what it boils down to.

Speaker 2: 15:14

That's great, laurie. It's a good time to put a little word in for one of the things we're doing this month in 2024. And JAVMA and AJVR is forming a statistics working group, and so we're going to publish little vignettes like one one, one pager each month Once we get rolling on. How do you do a sample size? Why you should use confidence intervals instead of relying on p values, because many of us, not just as researchers, don't know maybe the optimal way to do statistics, but as reviewers as well. So we're really excited about that. So thank you for validating what we think is important. Yay, I'm glad to hear it.

Speaker 1: 16:00

Yes, we'll be on the lookout for that, and this next set of questions is really important for our listeners. The first one is going to be on the veterinarian's perspective. What is one piece of information the veterinarian should know before discussing canine parbovirus monoclonal antibodies with a client?

Speaker 3: 16:18

Well, I have to say that probably the most important thing for the veterinarian to remember with this is to give it on board as fast as possible, just as early as you can in that course of disease. As soon as you have a positive snap, your next step should be to reach for that monoclonal antibody and then begin all the rest of your standard care treatments. The thing is, if we wait too long, right until we see massive bloody diarrhea or things like that, by that time our lymphocytes might be just decimated. So speed, that's probably the key for the veterinarian.

Speaker 1: 17:02

Thank you. And then now shifting to the client's perspective, what is one thing clients should consider around canine parbovirus monoclonal antibodies.

Speaker 3: 17:12

Well, you know, one of the big things for clients is always the sticker shock, right? How much is this going to cost me, doc, and this particular product? I believe the price point is around $200 per dose, and that can really set some clients back, but I think what they need to keep in mind is that giving this $200 dose may shorten their dogs' hospitals to stay by a day, or maybe even more, and maybe they'll be able to care for their dog at home on an outpatient basis, and so it might cost more now, but it's going to be a good investment in the long run and I think it will give you a better outcome, which is really what we want more than anything.

Speaker 1: 18:01

Yeah, $200 is just like a drop in the bucket of these parbovirus bills. I mean, I've seen them. I feel like no one really unfortunately leaves less than the thousands just because of the extensive support of care, monitoring, hospitalizations. Yes, yes.

Speaker 2: 18:16

I hear another manuscript coming, laurie the cost effectiveness of monoclonal antibody plus support. Yeah, obviously, as you said, it's not a miracle, but I hear another manuscript.

Speaker 3: 18:28

Thanks. Thanks for planting the seed, Lisa. I'll add it to the very long list.

Speaker 2: 18:35

Well, thank you so much. Like I wish I had you as a you're my advantage, so it wouldn't have worked. But as an immunology teacher you clearly have great passion and examples. So really thank you so much, and I'm sure our listeners are equally as excited. Thank you, lisa. That means a lot. As we wind down a little bit, we like to ask a fun personal question. And so, laurie, what is the oldest or the most interesting item in your desk drawer?

Speaker 3: 19:02

The most interesting item. Okay, so I have this in every desk, right, I have a desk at home and I have my desk here in the lab and everyone. I have a little cheat sheet to the shortcuts for French diacritic marks, right, you know all the little accents and the little tails underneath the seas and things like that, and it's just really important to me to be able to write in French correctly. And so, yeah, I can never remember the shortcuts, so I have a little cheat sheet.

Speaker 1: 19:37

That's really cool. Do you speak French? Yes, oh, that's excellent, very nice. Yeah, no, that's really really cool, though, thanks for sharing, laurie, you're welcome, and just thank you again for being here today and sharing your really fascinating study with our listeners. Again, like we said, this could be a game changer for this horrible disease, so thank you.

Speaker 3: 19:58

Yes, and thank you so much for accepting it for publication.

Speaker 1: 20:02

And to our listeners. You can read Laurie's article in French Alma or on our journals website. I'm Sarah Wright with Lisa 40 a. We want to thank each of you for joining us on this episode of the veterinary vertex podcast. We love sharing cutting edge veterinary research with you and we want to hear from you. So thanks for reading and review on Apple Podcasts or whatever platform you listen to.