Extralabel Rabies Vaccination: Serologic Response Across 28 Mammalian Species

0:00Every vet knows that cats love to get into trouble. But when your patient's experience urinary issues, they need Hills Prescription Diet CD Multi-Care Stress Cat food. With therapeutic nutrition formulated to reduce the recurrence of FIC signs by 89%, dissolves through vitestones in as little as seven days, help manage stress and improve social engagement, your patients can get back to feeling good, and getting up to no good. Intended for veterinary professionals. Welcome to Epic Award-winning veterinary vertex the AVMA Journal's podcast, where we delve into behind-the-scenes look with manuscript authors. I'm editor-in-chief Lisa48, joined by associate editor Sarah Wright. Today, we're discussing the serological response to extra-label use of preineral rabies vaccine and mammalian species with our guest, Ryan Wallace. Thank you for joining us, Ryan. Thank you so much for inviting you back on the podcast. I'm happy to be here. Yeah, it's great to have you back.

1:01Ryan, in this study, what prompted you to look at extra-labeled rabies vaccine across so many million species? And what are the practical problems that this off-label gap created for zoos, wildlife rehab, and zoological companion animal veterinarians? Yeah, so maybe for just a little bit about my background, I leave the rabies program at the US Centers for Disease Control and Prevention. We have two kind of critical roles that are related to this study. One is we oversee the National Rabies Reference Laboratory, which is a network of over 130 academic, agriculture, and public health labs that offer animal rabies testing. And we'll say we have the world's most robust animal rabies surveillance system, testing far more animals than anyone else in the world. So our CDC program oversees that network. And there are also the National Rabies Surveillance System, so rabies is a notifiable disease.

2:03And so when states do get reports of rabies in animals or people, that information is notified to us. And my group coordinates that. And every year, publish an annual report in the Journal of American Environmental Medical Association. So kind of in that role that I have, I and a few other people on my team answer about 2000 public inquiries a year related to rabies. And I only do rabies. So I think I'm one of the few people in the world that like 40 hours a week, probably more dedicated to rabies, answering rabies questions, doing rabies studies. And so about 2000 times a year, a state-owned department, agriculture, John Q. Public, they're reaching out and asking a rabies question. And a good chunk of those questions are what to do when an animal that is not one of our species that has a licensed rabies vaccine product, either becomes exposed to rabies or fights a person and is now being assessed as potentially having rabies.

3:07We have excellent guidance in the NASPHB rabies compendium that hopefully all of our US veterinarians are well aware of. Excellent guidance for what to do with a vaccinated dog cat, ferret sheep, you know, our common pets and livestock. The guidance for what to do when an animal has been vaccinated off label is very vague in case by case. So part of like the inspiration for this is because a big chunk of my time is spent dealing with these ad hoc situations, the spoke recommendations, the grazo. I as part of my job keep up with the rabies literature quite well. And for years, I felt quite confident that off label, extra label, vaccination does confer broad immunity in mammalian species. So oftentimes I am providing these papers or recommendation to our state health departments that it is okay to observe this off label vaccine in a day.

4:14I'm for a while or treat them similar similarly to how you would treat a vaccine dog cat, but I have not had a very good citation, you have to plumb them to. One other thing was happening around, yes, so that's been happening for years. We have not had that clear guidance and we, you know, lots of people have asked for it. Some colleagues of mine who ended up being co authors on this paper out of Germany had just completed an exhaustive literature search on lab animal studies on vaccinology of rabies. And I had the pleasure of reviewing that paper and saw that they had over a thousand research articles already identified and abstracted and sitting in a database ready to answer additional questions. So I reached out to them and said, hey, do you think we could use that your, your exhaustive literature search to also address this question about extra label vaccination. They said yes and we were off to the races with this study.

5:16Thank you for your second part of that question about the practical problems. I think I sort of alluded to it, but to be really clear, there are really, there are two very real world everyday issues that I hope this paper starts to provide clarity to one is my non dog cat, whatever mammal, has just a, he's vaccinated off label, but he's just been exposed to a rabid raccoon. What do I do? This should prove this study and the results we found should provide state public health authorities with some good evidence to feel confident that there are options other than euthanasia. If your animals unvaccinated, euthanasia is probably the best option in those situations. And then the second one as I alluded to my off label vaccinated, you know, insert any of the 6000 mammals that exist in the world. You know, has now bitten me or my neighbor joining to euthanasia that animal. And again, this study should provide a lot of confidence for options other than euthanasia.

6:25If you have to caution though, until regulations change, you know, that this is all just scientific evidence to support public health decision making. Yeah, really great practical information in this manuscript for our clinicians that see non traditional species. Additionally to the rabies manuscripts that your groups, Simmons are always very highly performing in jacquemage is always appreciate to it's very cool to see the attention that they receive and how many people are reading them citing them as well. They're also very impactful to in this colleague community as well. Yeah, there's really no better as a veterinary epidemiologist rabies is the absolute best field to be in. I mean, we deal with, you know, the zoonotic aspect, purely the animal aspect. When there's a human case were involved. But java is our go to journal anytime we have these studies that were really targeting the US veterinary professionals. Yeah, we really appreciate that there's some of our most highly read and cited as you probably know it's obviously critical for our profession.

7:29Now we're really happy to hear that. Back to your article, over 84% of animals had protective antibody titers after primary vaccination. How did that compare to what you expected? So I like I said, I do keep up with the literature. So all these piecemeal little studies that have come out over the last 20 years or so have largely all shown. High serial conversion after primary vaccination. You know, in these off label species. So going in, I was quite confident we should see that you know off label vaccination is is comparable or at least very close to what we see for the licensed animals. Primarily, and as we chose your dogs as the gold standard comparison. I was a little, a little surprise, not totally surprised, but a little surprised that we did see significantly lower serial conversion rates and some of our larger mass species, notably elephants and bears.

8:39And then we also saw lower serial conversion rates in our tiny species, the bats and I think there are explanations for why that occurs. And I don't think it really cast doubt on the effectiveness of modern day cell culture commercially available rabies vaccines. But for years, we've known there is a bit of a dose body mass, you know, association with with this vaccine. Right. Along with the protective antibody titers, the tighter persistence dropped to under 64% I think by six months. What's the practical implications of that drop in tighter? So all vaccines. Display a pretty typical immunologic curve. So you you vaccinate and hopefully within a few days. If it's a antigenically competent vaccine, your tighter goes out. The goal of your immune response is to make those memory BNT cells. It's not to keep a high tighter forever.

9:42The goal of especially rabies vaccine is that when you're exposed in the future, those BNT memory cells can quickly proliferate and get a sky high antibody tighter. That is what protects animals people, you know, from from getting rabies. So it is expected that over months after especially primary vaccination, tighter will fall. The fact that 64% fell below or we're at 64% you know, three, six, nine months afterwards. Not very surprising and with such a wide array of species and study designs. I also wasn't that surprised. But what I think the reader should draw their attention to is the boost ability that was demonstrated in a subset of these studies where I think it was something like 89 to 90% of animals that then got a second vaccine showed that anagnestic response.

10:45And that is spot on with what we see with our licensed species and that anagnestic or booster response is what we look for to decide if an animal is likely to survive infection. I've never heard that we're boost ability like that. I might have just made it up here. I'm not sure. Ryan, it always intrigued me personally that I would vaccinate it in vet school in the 80s and then had my titers checked yearly and my titers stayed within the recommended range. Why, why don't we do that in animals? I've never understood that. So the there are different recommendations, especially humans, there's different recommendations based on your risk of exposure to rabies virus. And so if you're in an occupation where you might be exposed to rabies and not recognize that that exposure has occurred, then we're concerned you're not going to go get that booster.

11:47So we're going to mount that anagnestic response and be protected. And for those occupations, we do rely, we do want to ensure that you have a continuous the high circulating anabiot virus. Sorry, antibody tighter. Primarily our laboratory, our laboratory diagnosticians that are working with rabies virus on a daily basis, they get a little nick, they walk through the freezer and get scratched by a carcass that's in there, which these all happen, we got calls up this old time. They might not necessarily think they need to go get their booster vaccine, but they get these tighter checks and they are assured that they have high, you know, certain thing everybody. Also ensures for our people that if they do have a change in their immune system that we're going to detect that relatively quickly and they can make their occupational decisions based on that information. In animals, you know, if they're well cared for kept inside or at least the monitored by a responsible owner, they really shouldn't be having unrecognized rabies exposures when those exposures happen they can reliably get boosters.

12:59I'd say the other other argument I would put against treating animals, they would treat people is just the cost. If anybody has had to pay for a tighter for their animal, they're not cheap, especially compared to just getting your rabies booster. You know, a large population of animal owners opting for that tighter route, the cost would be quite high. Ryan, I have a question for you for some people I've talked to you before and trying to convince them that their indoor animals still need to be vaccinated for rabies. So as long as it comes to you and they say, you know, and will never goes outside, I don't understand how it would get rabies. I'm not going to vaccinate it. What do you say to those people? Bats, bats love to live in our house. That's our number one babies, Rosa, for in the United States, and especially indoor cats, they are experts at catching bats. So I think you can probably talk to any state public health veterinarian, they'll dozens of examples of rabid cats that largely stay indoors or the calls from concerned owners where they're found their cat chewing on a dead bat in their house.

14:07So that's me as the number one risk for pets that largely stay indoors. You cannot guarantee that bats won't get into your house. Oftentimes, people are very delayed in recognizing a colony has moved in and usually your pet, especially a cat that's an expert at hunting these things, is the first indicator that a lot of homeowners get that they do have a bat problem in their house. But I think that's probably the best example of why we can't control wildlife and your pets are the frontline of that wildlife interaction. We need to make sure that they are protected. If you don't care about yourself for your pet, make sure they at the frontline of this are protected. Yeah, I definitely had that experience where the cats were told us what was going on in the walls. Ryan, how should the results of this study might, how might they change quarantine exposure protocols for vaccinated non domestic animals?

15:10Yeah. I mean, we all, I think everybody, all the researchers, everybody writes papers for java that's listening to this. I'm sure our hope is that our work eventually impacts how we operate as a veterinary community or through regulatory actions. One other thing I didn't say earlier about the kind of impetus for the study, not only had some colleagues of mine already curated this massive database that was perfect for for implementing the study. I and several of the co authors are part of the NASPHB rabies compendium, which is currently reviewing reviewing the national guidance to see where updates can be made. So another reason they were thinking, well, it's timely and we need to get this done quick is because we wanted this data synthesized and published so that we could consider it for updating the NASPHB compendium national rabies.

16:16I don't want to give away too much and discussions are still ongoing, but I can say this this study and a few other pivotal studies that have come out in the last five to 10 years are being considered for some pretty big updates to us, rabies guidance. Well, Ryan, thank you so much for joining us. It's been a pleasure chatting with you about rabies and learning more to about this really robust study as well. Yeah, thank you, Ryan. Thanks so much for having me. For listeners and viewers, you can read Ryan's article in Javna. I'm Sarah Wright with Lisa48. Be sure to tune in next week for another episode of Veterinary Vertex. And don't forget to leave us a rating and review on Apple Plod Pias or ever listen.