Episode 30: Immunology with Dr. Trisha Rettig

Laura and Judi have a conversation with Dr. Trisha Rettig - a researcher on immune response for NASA.

About Dr. Trisha Rettig: Dr. Rettig’s research focuses on the immune response to vaccination in space (in fact, she’s sent mice to space to study this!). Dr. Rettig is an expert on immunology, which is the study of the immune system.

Dr. Rettig gives an overview of what an immune response is, how it relates to vaccinations, and the difference between innate and acquired immunity. Laura and Dr. Rettig also discuss the specifics of titers and what breeders should consider when vaccinating their dogs.

Transcript

Laura Reeves [0:40] Welcome to the Good Dog Pod! I am your host, Laura Reeves, and I’m pretty excited. We’ve got a very interesting conversation today. Dr. Trisha Rettig is a researcher on immune response for NASA. (You guys!) And Dr. Judi Stella, who’s the Head of Research and Standards here at Good Dog! We’re going to talk about vaccines and vaccine response and titers—and all the kind of stuff that we can do together to get the best health for our dogs long-term. So, welcome, Trisha. How are you doing? 

Dr. Trisha Rettig [1:11] I’m doing great! Thanks for having me. 

Laura Reeves [1:13] Thanks for joining us! Why don’t you give us a little bit of background? This NASA thing—that was exciting to hear about. 

Dr. Trisha Rettig [1:22] Right? Who doesn’t want to hear more about space mice? I know! They’re absolutely amazing. My PhD and then my postdoc research (that’s what you do after you graduate) has focused on the immune response to vaccination in space. We actually had mice that lived up on the International Space Station and were the first animals to be vaccinated in space. We have vaccinated humans in space, but these are animals. My research studied how we build an antibody response—an antibody is part of the immune system—to vaccinations. People want to know why. Because space affects 300 people, not the rest of us. The idea is that it’s a very stressful environment. By doing this research in a very stressful environment, not only will it protect our astronauts (which is really important, especially as we move towards going to Mars in these really long-term missions) but it’s also a model of stress for us down here on the ground. When we’re stressed out, how does that affect our immune system? It’s been the coolest thing to see a rocket with your own experiment going up into space. It’s the coolest thing! It’s absolutely amazing. I could talk forever about space mice. They are amazing. 

Laura Reeves [2:44] Space mice seems like a whole other podcast all by itself. For today, let’s talk a little bit about immunology. This is suddenly in everybody’s purview, so we’re going to talk about it in relation to our dogs. What do we mean when we talk about immune response? You get a vaccine, and you get an immune response. Can you talk about innate versus acquired immunity and some of those sorts of concepts?

Dr. Trisha Rettig [3:14] Sure! Real quick overview: Your innate immune response is the first line of defense whenever you come in contact with a pathogen. Whether that’s you get a cut, you inhale a virus, you eat a bacteria—whatever it is, your first response is your innate immune response. This is a nonspecific response. It works the same, whether you’re fighting a cold virus or you’re fighting the flu virus. The basic response is the same. This first line of defense basically tries to put the cap on the infection as fast as it can, but it also then recruits in what’s called your adaptive immune response. This is where the antibodies that I talked about earlier come from. Your adaptive immune response has your B cell (which produce the antibodies) and your T cells (these are what specifically focuses on whatever infection you’ve had). If we’re talking about vaccines and we’re vaccinating against parvovirus, your adaptive immune response builds that specific immunity against parvo. That’s why we do vaccines, and that’s why we’re built on this idea of doing vaccines and creating this highly specific response. Once your adaptive immune system has kicked in, you’re basically protected—not necessarily for life, but for a long time. This is why we don’t get the same infections twice. That’s the result of your adaptive immune response. By doing vaccines, we’re trying to build that adaptive immune response without having to get sick, which in this case, can be lethal for a lot of these infections we’re trying to fight.

Dr. Judi Stella [4:53] That’s a great overview. Can you just talk a little bit about how vaccines do stimulate the immune response and even a little bit about safety around those?

Dr. Trisha Rettig [5:01] When we inject an antigen—an antigen is either part of whatever it is we’re trying to fight (we’ll stick with viruses) or the whole virus—and we inject that and by itself, it is safe. By injecting just the little piece—and there’s a bunch of different types of vaccines that would be its whole own discussion—we can make sure that you can mount a safe immune response to it and not have an entire infection. By doing that, we can build up that adaptive immune response and make sure that it’s safe. By doing just a little, tiny part of it or a virus that’s been killed (so we know that’s not able to replicate in you), we can mimic the effects of getting an infection without actually having to get the whole infection. 

Dr. Judi Stella [5:54] We hear online about titers. I think there’s some confusion about when you would do a vaccine versus when you would do a titer. Can you talk a little bit about what a titer is and what exactly we’re looking at and measuring and when we would incorporate that into a wellness plan?

Dr. Trisha Rettig [6:08] What a titer is looking at is actually measuring those little antibodies. Antibodies are produced by B cells. These antibodies circulate throughout your bloodstream, and they circulate throughout your body, and they’re always looking for things to bind to. That specific response—those antibodies only bind to, for example, the parvovirus. By binding, they’re able to recruit the immune system really quickly. They’re able to clear that infection before it ever becomes a problem. What titers are measuring is the level of that antibody in the blood. What that tells us is how much of it is circulating. We use it as a measure of memory. It is not the exact same as immunological memory. When you mount this adaptive immune response, your body produces these memory cells that go to live long-term, usually in your bone marrow. For our dogs, a lot of times they live their whole lives. For humans, it’s a little different because we live to be older. That memory is then what protects you. By measuring the antibodies in the system, we’re able to tell whether or not you’re protected from a specific pathogen. We use that as a measure of memory, but it’s not an exact measure of memory. We want to use those titers that you see, for example, if our dogs ever responded to a vaccine. I do titers right away after I get my puppies. So we have our puppy plan of when we’re doing our vaccines. As part of that, I have titers planned out. Did my dog actually respond to the vaccine? Because we have dogs that are called non-responders, so it doesn’t matter if you’ve given them the vaccine; they can’t respond to it. Or perhaps they just responded poorly and we have to, you know, go back and double-check. Just because I gave  a vaccine doesn’t mean that I was given immunity to it—even though most of the time, that’s true. As we progress through the dog’s life, we can keep going back and doing those titers. I think the recommendation right now is every three years. You can keep going back and checking to see if that memory has faded, because sometimes it does, and it really depends on the animal whether or not we need to vaccinate again to make sure that they’re really protected. Keeping it as part of your plan right away to make sure that your puppy was protected and then making sure, as they get older, that they haven’t faded. I have a nine-year-old right now. Her parvo titer is low. She does need to go in and be re-vaccinated. But my three-year-old is fine. He doesn’t need one right now. As he gets older, we’ll have to double-check and make sure that that’s still there. 

Dr. Judi Stella [8:44] Basically, the recommendations now are pretty much every three years for most of the vaccines. One thing that you could do if you’re worried about vaccinating, you could incorporate a titer instead and decide whether or not the dog needs to have a booster periodically throughout, instead of actually doing the vaccine. But we only do that for certain things, right? We don’t do that for rabies.

Dr. Trisha Rettig [9:04] We can do rabies titers. They aren’t accepted in the vast majority of states. I don’t know the legal ramifications, all that. You can titer for—I believe—adeno, parvo, and distemper. We don’t consider common titers for other things. You can titer for things like lepto and lyme, but they’re usually done as confirmatory, like when your dog is sick, rather than the dog is actually maintaining a boosted immune system to them. So, yes, when you’re about to give your every-three-year shots, you can go grab titers and you can make some calls. All this depends on your living situation and what your dogs are exposed to. Is parvo endemic? Are your dogs running into distemper? The life of a dog who lives in downtown New York is very different than the life of my Golden Retriever who goes out hunting in the field. What he’s exposed to is very different than what a different dog may be exposed to. You obviously have to work with your vet and find what’s the best bet going forward. 

Laura Reeves [10:05] Trisha, just a quick question. When you grab a titer, pull a titer, you’re pulling blood, right? This is a blood test that your veterinarian is going to run. 

Dr. Trisha Rettig [10:14] Yes. You don’t need to send whole blood. They just send serum in. You don’t have to pay for the expensive overnight shipping and everything. You can just send in a quick vile, spin it down. You can submit them yourself if your vet doesn’t do them. My vets have always been good about it, but you can definitely submit them yourself to: the University of Wisconsin-Madison does them, Michigan State does them, I know IDEXX does them. You’ve got some options if your vet doesn’t do it. 

Laura Reeves [10:42] There’s a variety of labs that breeders can work with, or owners.

Dr. Trisha Rettig [10:46] Yup!

Laura Reeves [10:47] I think one of the things that we want to think about is, as dog breeders and also as owners, when we’re talking about these vaccines or titers or however we’re going to manage our dog’s health the best, looking at those different options. You can talk a little bit about why this is important? Drill down on that. I also wanted to pick up on one other thing that you were talking about: the dogs who are non-responders, because there are breed-specific things that go with that. Can you dwell on that just a little bit before we go into how we use this and why it’s important? 

Dr. Trisha Rettig [11:27] I do not have a non-responder breed, so I am not super into all of this. Basically what happens, to my understanding, is that when your body is dealing with an infection, it has to be presented to other cells. We have these cells called antigen-presenting cells. All of your cells in your body can also present, for example, viruses, because it’s not just your immune cells that can respond to viruses. All of your cells in your body can be infected with a virus. All of our cells have this ability to present stuff that’s on the inside to the outside. Some dogs and some people—they’re not able to present that specific part of the virus or the infection to the immune system to get it captured. We have these things in humans that are called HLAs. They’re able to present tiny bits of what’s inside to the outside. I believe what happens is some of those dogs don’t have the ability to present that properly, so it’s a failure in the presentation to the immune system. So they’re not able to respond properly. Those things are genetic. That’s why it’s stuck in specific breeds. Or we see in people—this is much better studied in people—this is why we see specific genotypes of people or people from a specific region have a specific ability to respond or not respond because those things are genetic and because that’s how they’re transposed and go through the system, basically. 

Making the choice, as a breeder: Should you breed a non-responder? That’s something you need to be weighing very severely. My personal opinion, I would not be continuing on a non-responder. There are dogs that will be non-responders for their entire life. There are some dogs that just fail to mount an immune response to the vaccine. Those are two different things that should be weighed a little differently. Definitely breeders need to be making some decisions: Should you continue with non-responders? Do I want that in my lines?

Laura Reeves [13:39] I know that Rottweilers are actually a breed that is very specifically associated with this. In all honesty, I grew up with Clumber Spaniels. Clumber Spaniels have some sense of this as well—just the ones I know of, off the top of my head. 

Dr. Trisha Rettig [13:55] It’s definitely that there’s genetics. In dogs, it’s DLAs—not human, it’s dog. There are definitely some parts of the immune system. They come from mom and dad. It’s genetic, so making those decisions—do I want this in my lines? I don’t have non-responders, so I don’t know all the specifics behind it, but it is definitely something that people should be aware of. This is, again, why those titers are so important. A lot of people follow the 6/8/10 or 8/10/12, but even if you’ve given three vaccines, if that dog is a non-responder and they come in contact with parvo, that dog could lose its life because of that. It’s important to titer, especially after those puppy vaccines, to make sure that you don’t have non-responders. To work with—I know University of Wisconsin does a lot of this—those non-responders and figure out: can we get them to respond? That’s something you need to work on with your vet. 

Dr. Judi Stella [14:55] With the non-responding, is that all associated with specific vaccines?

Dr. Trisha Rettig [14:59] I have no idea. 

Dr. Judi Stella [15:03] Some vaccines are different, so I’m wondering if, in some of those cases, whether just switching to a different type of vaccine would make a difference. 

Dr. Trisha Rettig [15:10] In dogs, we don’t have a ton of variety of different vaccines for most of our stuff. In humans, we’ve moved to a lot of this recombinant technology, so this idea that we just take (for example) an outer-surface protein of something and we put it into a vaccine and then your body is just learning to respond to that outer-surface protein. Honestly, when I was doing research for the upcoming webinar, I ran into the fact that we don’t seem to have a lot of recombinant technology approved in our dogs yet. There may be some possibilities for getting some of those non-responders to respond better by using some recombinant technology instead of—we use a lot of modified lives, which are good vaccines. We use a lot of killed for things like rabies. We don’t want to be injecting modified lives. We need to be using killed  vaccines. I have seen recombinant rabies vaccines, but I haven’t seen those really gain approval yet in the US. I think they’re out there, and they’re working on them, and that would be a possibility. They just don’t seem to be very highly available. 

Laura Reeves [16:21] I think that was another one I wanted to touch on a little bit more. I think it’s poorly understood, generally. I’m old enough and long enough in dog breeding to remember when parvovirus first arrived. All we had when we started was some level of modified lives. The difference between the modified lives vaccine and when they were able to come up with a killed vaccine—can you talk a little bit more about how that operates in the dog’s system? 

Dr. Trisha Rettig [16:51] Modified lives are the best for getting a good mounted immune response. They are also the most likely to cause side effects, which can cause some of the problems. What a modified live is is it’s basically a virus that’s been what we call attenuated. It’s been passaged in the lab over and over and over and over again. Basically what this means is they just keep growing the virus for weeks, months, years, however long it takes so that the virus is still able to infect the host (which is why we get side effects), which is why we get uncomfortable, because our body is actually fighting a real infection. But it’s not dangerous. It’s getting a mild version of the infection. You don’t have symptoms aside from what you would get in a normal immune response, when you get a cold. We just have normal immune responses. This is how our body responds to things. You get tired. Maybe you get a little bit of a fever. It’s a little sore. Because the immune response is actually happening. By using these modified lives, these viruses are actually able to replicate inside the system. On the other hand, the killed vaccine is a vaccine where they’ve grown the virus and they’ve inactivated it somehow—whether that’s heat treating or chemicals, however they’ve decided to inactivate that virus. Now that is able to enter the body, and the body sees it as foreign but because it doesn’t replicate, the immune response mount can be different, because it’s not replicating and going through a normal immune response. In some cases, that’s all we have. In some cases, that’s safer. We mentioned rabies. Having a modified live of rabies is a very dangerous thing. You need to have a killed vaccine of it. Those killed vaccines are, a lot of times, the first things that come out because they basically just have to inactivate whatever the virus is. It gives us different ways of approaching it, but as we’ve discovered, some vaccines just don’t work. There’s millions of different things that have been tried for human vaccines, for dog vaccines. This should work, this should work, this should work—but for whatever reason, it doesn’t mount a good immune response. It doesn’t mount a protective immune response, even though we guess that it should. There’s a lot of failed attempts behind everything that we do see out on the market. There’s a lot of stuff that didn’t work.

Laura Reeves [19:20] That’s really, really good for people to be able to understand. Judi, did you have anything more on that? 

Dr. Judi Stella [19:24] No, I think you covered it pretty well. Interesting conversation. 

Laura Reeves [19:28] Excellent. And a very interesting conversation that we are going to pursue further in webinars coming up! I’m very excited. 

Dr. Trisha Rettig [19:36] I’m very excited! 

Laura Reeves [19:38] In the webinars that are coming up through Good Dog, people will be able to actually ask questions. Yes, Judi?

Dr. Judi Stella [19:43] You’ll be able to submit questions ahead of time and then through the chat, like we do with our live webinars. We are going to have two of them. One is going to dive a little bit deeper into this. Trisha’s got some cool graphics that she’s going to show about how the immune response works and talk a little bit about nomographs and a little bit more about titers and things. And then we’re going to follow up with one that’s going to really talk to people about how do you come up with a wellness plan that is best suited for your dog, your dog’s lifestyle, and where you live in the country. As Trisha alluded to, different dogs have different risk factors for different diseases, so we should take that into consideration and have these more tailored plans. We hope everyone will join us for those in continuing this really interesting conversation! 

Laura Reeves [20:28] Excellent! I think that one of the things that I’m really excited to see continue in those webinars and carried forward is talking about tailored vaccine plans—specifically things like leptospirosis. Dr. Jean Dodds is another one who has created the “everybody’s got their own” plan. What is your risk factor? Is this a poor vaccine or a life-threatening vaccine or a rattlesnake vaccine? If I live in New York City, I probably don’t need a rattlesnake vaccine. These are the kinds of things I think are super important for breeders to look at, to understand what is the best possibility to keep their dogs healthy without just blowing up the immune system. 

Dr. Trisha Rettig [21:17] There’s definitely strategic choices that we can make. Look at it as the same thing for humans, too. I didn’t need a lot of vaccines until I went abroad to a foreign country and all of a sudden, there were things that I could be exposed to that I wasn’t going to be exposed to here in the US. It’s the same thing for our dogs. It’s important to be informed when you’re making those decisions, and that’s what I want to do, and that’s what I want to bring to the forefront. Here’s what the immune system does. Here’s what a vaccine does. Here’s how we respond. Here’s what the things are that we can vaccinate against. How can you work with your veterinarian to make the best choices for your dogs? 

Laura Reeves [21:58] That, I think, is going to be great. Thank you so much. Really appreciate it, Trisha! Thanks, Judi! Thanks for joining us. Look forward to seeing more of this on the webinar. Everybody, check it out! Watch this space.