Bird Flu Outbreak ‘Very Concerning’ as Influenza Season Ramps Up

Influenza season is ramping up, SARS-CoV-2 and respiratory syncytial virus 
(RSV) continue to evolve, and the bird flu outbreak is gaining steam in the 
United States. Against this ever-changing landscape of infectious disease, 
this episode centers on viruses and vaccines. Our guest is Jenna Guthmiller, 
PhD, assistant professor in the Department of Immunology and 
Microbiology at the University of Colorado School of Medicine. Guthmiller 
discusses the H5N1 outbreak, evolving viruses, the history of pandemics 
and the potential for a universal vaccine.

Transcript

Chris Casey:

Welcome to another episode of Health Science Radio, where we talk with researchers at the University of Colorado Anschutz Medical Campus about the ways they are innovating and advancing healthcare. My name is Chris Casey and I'm the director of digital storytelling in the CU Anschutz Office of Communications. It's a pleasure once again to be joined by my co-host here in the historic Fitzsimons Building, I might add, by Dr. Thomas Flagg, our vice chancellor for research.

Thomas Flaig:

The pleasure is all mine.

Chris Casey:

And how are you doing on this fine wintry day? Today, I believe, marks our first measurable snowfall in the Denver area for the season.

Thomas Flaig:

On campus, we call that First Snow.

Chris Casey:

Oh, yes.

Thomas Flaig:

And there is a budding tradition here, it started really with some of the student groups, to celebrate the first snow, some hot cider and some people on campus today got a new Anschutz First Snow scarf.

Chris Casey:

Besides snow, we are also entering the flu season, which is just ramping up. And today, we'll be talking about viruses and vaccines. We'll discuss some of the latest research into how our immunity against rapidly evolving pathogens, such as the influenza virus, develops and can be targeted by next-generation vaccines.

Our guest is Dr. Jenna Guthmiller, an assistant professor in the Department of Immunology and Microbiology at the CU School of Medicine. Jenna received her undergraduate degree from South Dakota State University and her PhD from the University of Oklahoma Health Sciences Center. She conducted her postdoctoral research at the University of Chicago and established her lab here at the University of Colorado in 2022. So welcome to Health Science Radio, Jenna. Glad to have you.

Jenna Guthmiller:

Yeah, thanks for having me.

Chris Casey:

And also thank you for braving the weather. And so let's just perhaps start our conversation about laying the landscape about viruses. I believe you had a question about that, Tom.

Thomas Flaig:

As you point out, 'tis the season where a lot of people are thinking about influenza and their vaccines and what's going on, but I would say in the news over the last many months, there's been talk about bird flu or avian flu. So maybe it'd be helpful just to start out by talking about influenza, types of influenza, bird flu, seasonal flu, and just kind of add to that general understanding of the topic.

Jenna Guthmiller:

Sure. So when we talk about influenza or just commonly referred to as the flu, there are two types that largely infect us. Those are influenza A and influenza B. Influenza B is a pretty human-specific virus, so that tends to cause seasonal outbreaks amongst humans, but influenza A is a much bigger beast in that it can infect a lot of different hosts and there are different types of it that can infect these sort of different hosts.

So when we talk about avian influenza or bird flu, we are specifically referring to viruses like H5N1, which is maybe something you've heard about in the news, versus the seasonal influenza viruses or influenza A viruses that infect us are H1N1 and H3N2. And so those H and N sound very intimidating. We have a lot of different ones that we are aware of. There's 19 different Hs and 11 different Ns.

Thomas Flaig:

Wow.

Jenna Guthmiller:

So there's a lot of diversity, but fortunately, the only ones that cause or that have sort of a foothold in humans are H1N1 and H3N2, whereas birds get essentially all of those to a degree. And not only humans and birds can get influenza viruses, but a lot of other animals. So for example, if you guys remember back 15 years ago at this point, we had an influenza pandemic caused by a swine influenza virus, so it was the swine flu. So pigs are also susceptible to influenza viruses. So are horses, so are cats both domestic-

Thomas Flaig:

And cattle, right?

Jenna Guthmiller:

And cattle now. So certainly, I'm sure we'll talk about that further, but there's a lot of hosts for influenza and those do pose a threat to human health.

Thomas Flaig:

I think it's really helpful to talk through that a little bit because I think there are these different types. The seasonal is obviously something we humans worry about this time of year. A lot of people are asking questions about the seasonal vaccine and so forth. So what's the history of our approach to trying to vaccinate people against the flu?

Jenna Guthmiller:

Yeah. I mean, we can take the wayback time machine a bit.

Thomas Flaig:

Sure, we'd like that.

Jenna Guthmiller:

So influenza, as a virus, was first identified in the 1930s. That was the first time that anybody was able to grow it, and your ability to grow a virus is your capacity to study said virus. And as a result, understanding how you can grow a virus allows you to start to develop vaccines against it. And so as soon as people are essentially able to grow that virus, they're able to start making vaccines. Most vaccines at the time were inactivated viruses. So they took a virus, they grew it, and then they threw some stuff at it to kill it, and then that was what you got. And those were really the first flu vaccines.

One sort of fun fact, if you will, about the flu vaccine is that the first flu vaccines were made in the US with the US military in mind. And they were developed by Thomas Francis Jr., which is not a household name per se, but the other person that developed it was Jonas Salk, who was also the person that made the inactivated polio vaccine. So really, a pioneer in vaccine technology.

Thomas Flaig:

Oh, that's really fantastic. And so has our approach to making these vaccines changed over time? You talked about the method of essentially killing the virus and using that product to stimulate immune response, but has that changed over time? What's been the timeline of that development?

Jenna Guthmiller:

Yeah, for sure. So the first vaccines were late '30s into the '40s and it really became more public in the mid-'40s. And that technology is the main technology that persists with us today. So growing up a virus and then killing it is still, for the most part, how most of us are vaccinated year to year. That said, there's a few newer technologies that exist that are on the market. They just tend to take sort of a smaller percentage.

In one of those, you can make what is referred to as a recombinant vaccine. So you can just take one of the proteins of the virus and make that and immunize with that. In this case, it's that H protein that I mentioned, like an H1, H3. That's one type of vaccine. That's really been for about the last 10 years that that's become more common, but it makes up maybe 1% of people that get vaccines get that vaccine.

And the other type of vaccine that was approved in the early 2000s is a live attenuated influenza virus. The market name for this is FluMist. And so this is a virus still, but it's been attenuated to grow at lower temperatures, so below our body temperature. So it can still infect us, but it's not going to grow very well because our temperature is too high for it to really be successful. And those are noted for inducing nice mucosal responses because that vaccine is actually given intranasally, so in our nose.

Thomas Flaig:

So in both cases, whether it's the killed or the live attenuated, you want to have that exposure to the immune system, whether it's killed or attenuated, so that whatever is used in the vaccine doesn't necessarily hurt the host, or the person in this case, but stimulates that immune response, I guess.

Jenna Guthmiller:

That's the whole point of vaccines, yes.

Thomas Flaig:

Yeah. Maybe I just want to ask one more question here. The other thing that's I think somewhat unique about vaccines for flu rather than other things is that every year they need to decide what it's going to be and make it ahead of time. So a lot of people go to the doctor's office, get a vaccine, it's the same one off the shelf, tetanus, whatever. So there is this idea they have to think ahead and make a guess and then make the vaccine for that season.

Jenna Guthmiller:

Yeah, exactly. Going back into the historical context of flu, when they identified it, they didn't know that it mutates. So flu has this really remarkable capacity to mutate specifically to evade our immunity. It's very efficient at doing that.

So when they made the first flu vaccines, they said, "Great, we've solved influenza virus as a disease. We should be fine." But what they quickly learned is that a vaccine from five years prior is no longer providing protection, and that's really what led to this idea that you need to be updating the vaccines to be hitting viruses that are going to be circulating, which is still a little bit of foreshadowing, a little bit forecasting of what we think will happen, which none of us are... We can't tell the future, but we try to learn what is going on. Specifically for North America, we look at what's happening in South America and vice versa. When they're making vaccines for the flu season, I say South America, but the Southern Hemisphere, they look at what's going on in the Northern Hemisphere to decide what strains are circulating and would be good targets for vaccination.

And so yeah, we do have to work to update the vaccines. I don't need to bore you with all of the ways that this is determined, but there are methods that we use. Some are better than others, but we think that by combining a lot of different ways of looking at the problem that we can potentially better predict what will happen.

Chris Casey:

And speaking to that, for this year's vaccine, Jenna, could you just explain what the strains are that this year's vaccine is geared toward? And isn't there one strain that's kind of tailing off that was in the vaccine in recent years? And that one is now not part, it's now, instead of a quadrivalent, if I'm using the right terminology, it's like a trivalent vaccine?

Jenna Guthmiller:

Yeah. So up until this year, influenza vaccines were a quadrivalent vaccine, which means that they had four different strains that were incorporated into them. So there was an H1N1, an H3N2 component for the influenza A’s, again, since those are the ones that cause seasonal human outbreaks. But there's also two lineages of influenza B viruses, and these were respectively known as the B/Victoria lineage and the B/Yamagata lineage.

So, one thing I really like about flu is I really like geography. I like looking at maps. I like where knowing things are, and every flu strain is named after a location. So I was in Brisbane for a meeting last week and there's so many Brisbane strains, so I'm just like, "I feel like I'm really where history has happened." But anyways, I digress. So, a B/Victoria lineage and a B/Yamagata lineage.

And since then, we've actually gone down to a trivalent vaccine and removed the B/Yamagata lineage from the vaccine. And the reason for this is that there hasn't been a single B/Yamagata influenza virus case in the world since March of 2020. And so what we think likely happened is that this virus has potentially gone extinct as a result of the precautions that were taken due to COVID. And secondarily, because influenza Bs are highly specific to humans, those precautions of humans really squashed it as a virus. And even around 2020, it was only making up about 1 to 2% of influenza B cases. So it already was pretty limited in its spread. Those precautions, the fact that it was a human-only virus has potentially led to its demise.

Chris Casey:

I would like to jump over to the avian flu situation a bit here at the top because it was in the news a lot earlier in the year. In fact, I read a report that the avian flu virus affected like 90 million birds in the US since 2022, and then last spring, we had cases of it in dairy cattle, including here in Colorado.

I'm just wondering, is it quite unusual for that influenza A, as you described it, to jump to cows?

Jenna Guthmiller:

Yeah, so there is some historical context that influenza viruses can infect cows, but like most influenza viruses, it causes a respiratory disease. But maybe what you were starting to allude to is that this outbreak of H5N1 and the avian influenza virus that's killed 90 million birds, that virus is causing infection in mammary tissue in lactating dairy cows. So a very specific group of cows, a very specific tissue. It's really not causing respiratory disease.

Chris Casey:

Okay.

Thomas Flaig:

And what kind of disease is it causing then?

Jenna Guthmiller:

Yeah. So when an infection happens in mammary tissues, cows included, that can lead to something called mastitis. So that is just inflammation in the mammary tissue, which often leads to reduced production of milk. The quality of that milk, so it often becomes thicker, discolored, so more yellowish, not that nice white milk that you buy in the store, and it becomes more cellular, meaning that there's more cells in the milk, oftentimes because of inflammation in the tissue.

And what’s really remarkable about what we’re seeing with these outbreaks is that a single dairy cow, they’re going down to making maybe one gallon.

Thomas Flaig:

Oh, interesting. Yeah.

Jenna Guthmiller:

So their milk, not only is the milk changing, but the amount that they're capable of making is dramatically reduced. And that's really how it was identified. Unexplained mastitis reductions in milk production, they looked for everything that is known to cause this, and eventually somebody said, "Let's look at bird flu," and that was how they identified it.

Thomas Flaig:

And does that site of infection then have any impact on transmission or how it might spread to humans or other animals or things along those lines?

Jenna Guthmiller:

Yeah. So we still don't understand how it's transmitting. It's clearly, since it's not causing respiratory disease, it's not the typical sort of airborne transmission that we associate influenza viruses with. What we think is that milking uses what are called milkers. So they're essentially these automated robots that just milk, you put them on the cow teats and it milks that, and you just transfer that from one cow to the next cow. And potentially this could be how it's transmitting from cow to cow.

As far as across herds, what has also become apparent is that cows actually move a lot. They don't just stay on one farm. They actually move throughout the country depending on where they are in their cycle. So as you can imagine, in order to be a lactating cow, you need to have been pregnant and given birth, and then you will produce that milk. And oftentimes for lots of large dairy farms, it's not really feasible for you to do the breeding yourself and to feed that pregnant cow, literally. And instead, they ship it to places where there is abundant feed that it's easy for those people to do those procedures. And then once it's given birth, you ship it back. And that's how we think this is actually spreading is through these sort of interstate trade of cows.

Thomas Flaig:

Yeah, and I think there were some cases of transmission to humans. Is that through the milk per se then?

Jenna Guthmiller:

Sure. So actually, in the US, this year alone, there have been 44 confirmed human cases of H5N1. The vast majority of those have been either dairy farm workers or people that are culling infected chickens. Specifically, the H5N1 that's causing the dairy cow outbreak has infected over 30. So the majority of the cases this year have been identified due to dairy farms.

Why that's potentially concerning, so I think about 20ish of those have been dairy farm workers. There's been another nine in the state of Colorado. So what's happening is that the dairy cow virus is jumping back into wild birds, which then go infect poultry. And so in the state of Colorado this summer, there was an instance where it jumped back into wild birds and then it got into chickens. And it was the second week of July. I don't know if you guys remember that week. It was definitely the hottest week we had this summer. And I think what happened was people were culling infected chickens, they weren't wearing proper PPE. And as a result, the risk of heat stroke versus avian influenza, the cost-benefit analysis, I think made sense at the time, so yeah.

Thomas Flaig:

So the heat, PPE is their personal protective equipment, and so because of the heat and it's difficult to wear in the heat, people maybe weren't wearing that as steadfastly, and that maybe led to some of these cases?

Jenna Guthmiller:

Yeah, for sure.

Thomas Flaig:

Interesting.

Jenna Guthmiller:

And then we also know, just for reference, I grew up on a dairy farm. So also for reference, before you put the milker on the cow, you also have to hand-milk to get the milk flowing. So what happens is that that milk just splashes everywhere. And so what's been noted is if you take swabs basically of the walls of a milk parlor, you can find very high levels of virus. And so it's very feasible that it's getting to people just through environmental contamination.

And the other thing is that when you milk, you're not bending over to do this, you're actually standing at a lower level relative to the cows, and you're actually at shoulder-head level to the cow, so it's easier to do these things. And most of the cases that have occurred have actually caused conjunctivitis, so it's getting into the eyes.

Thomas Flaig:

Do you want to comment on this concept of antigenic drift and how it might apply to this situation or just more broadly?

Jenna Guthmiller:

Yeah. So I alluded to this before, but I didn't use that term. So antigenic drift is just the process of the virus evolving or mutating to evade our immune responses. And so this is just sort of a... We call it a drift because it just kind of happens over time. It's just drifting as time goes by.

Thomas Flaig:

And you compare that to an antigenic shift, which is a more serious sort of change.

Jenna Guthmiller:

Yeah. So antigenic shift, and oftentimes people get these terms confused, so one unique... I wanted to say, "Cool." I think it's cool. It's interesting.

Thomas Flaig:

Scientifically cool, right?

Jenna Guthmiller:

Yeah. A facet of influenza viruses is that they have a segmented genome. And essentially what that means is that every gene that will produce a protein of the virus is on its own piece of genome, if you will. So as a result, it has eight different segments that compose its genome. So that's the background we need.

So when you have two distinct influenza viruses that infect the same cell, what can happen is as it's starting to make new viruses, it'll just exchange those segments. So it'll just shuffle it around like a deck of cards. And what can happen is that the virus that you get out of that is entirely different than the virus that was put into the situation. And that is what we refer to as antigenic shift because it's a new virus that has been created.

Thomas Flaig:

And let's just go back for a moment. You're talking about this virus that was in cattle, got into birds, then shifted back and so forth. So how would you characterize that, that framework you're discussing?

Jenna Guthmiller:

Yeah, so we wouldn't use the word shift in that case.

Thomas Flaig:

Right, right. Yeah.

Jenna Guthmiller:

So certainly the virus that is infecting the dairy cows came from birds. We don't know entirely how it got to the cows, how it got into that tissue. We just know that it's happened. Okay? So that virus was actually the result of an antigenic shift last year, and then we don't know if that shift was necessary for this dairy cow outbreak. I'd probably argue that it's not. There's been a few studies using more historical H5N1 viruses, and by historical, I mean like two years ago, prior to that exchange that they've shown that that also is capable of infecting mammary tissue. So, it doesn't seem to be anything unique about that.

Okay. Moving forward in time, so the H5N1 virus in cows, as I mentioned, it is getting into wild bird populations again. We're also seeing infections in some odd animals. For example, barn cats. Barn cats that are drinking unpasteurized milk are getting infected, and oftentimes it's lethal in those animals. Also seeing it in house mice. We also think that they're probably drinking unpasteurized milk on those farms, and it's also causing a lethal infection.

Thomas Flaig:

Maybe just one point just for the public service announcement: Pasteurized milk removes any risks associated with this sort of milk, and the supply we have is pasteurized, just to make that point is my understanding.

Jenna Guthmiller:

Yeah, absolutely. So pasteurized milk, and this has been well-studied, if you take milk from one of these infected cows, which has very high viral titers, you pasteurize it through all of the conventional methods, they've tried all the different types of methods that are in our markets and our grocery store milk, every single time, it kills all of the virus. So it doesn't seem to be an issue that drinking pasteurized milk will lead to infections. Much more concerning if you're drinking unpasteurized milk.

Thomas Flaig:

Unpasteurized.

Jenna Guthmiller:

... so raw milk.

Chris Casey:

Thank you for adding that PSA. That was an important bit of information.

Thomas Flaig:

We don't do that enough on this show, I think.

Jenna Guthmiller:

So please drink pasteurized milk.

Chris Casey:

Yes, there you go.

Thomas Flaig:

Historically, pasteurization has been around for a long time and still seems quite effective, even in this situation.

Jenna Guthmiller:

It's a very simple thing to do to prevent a lot of diseases.

Chris Casey:

Jenna, just to start talking a little bit more about specific research you're doing here in your lab, so you've been working and your colleagues have been working toward a universal, as I understand it, a universal flu vaccine. Could you explain what's involved there and what would this potential universal flu vaccine do? Are we talking about something that could be protective to us from the flu for longer stretches of time, like maybe a couple, several years?

Jenna Guthmiller:

Yeah. So really, the goal of a universal flu vaccine is to make a vaccine that will provide protection independent of antigenic drift and shift. So, both these strains that pop up over time as the virus mutates, but also if there's a novel or a new influenza virus that emerges and causes a human pandemic, that that vaccine would also preemptively protect you despite us not knowing what that virus is. 

Thomas Flaig:

So you contrast that though with the current vaccines we have, this would be a different approach. Going back to our earlier conversation, there'd be utility of this longer term both in planning and production and use of it.

Jenna Guthmiller:

Yeah, absolutely. I mean, if it's one shot that provides protection against everything, that would be the ideal situation. So we don't have to be having this constant, what's circulating in the Southern Hemisphere and how does that inform the Northern Hemisphere and vice versa, and how do we stay ahead of it? By generating a universal vaccine, you could potentially get in front of everything well in advance, even the stuff that you have no idea what it is.

Chris Casey:

Well, that sounds ideal. And I would imagine this presents a raft of challenges to produce such a vaccine. Could you talk about some of the hurdles that would have to be cleared to get to this?

Jenna Guthmiller:

Yeah, no, you're right. I mean, obviously we don't have it because it is very challenging to do. And where you have to start is to understand what are the correlates of protection against influenza viruses? So what do we know about the immunity that we have that is correlated with us not getting infected with influenza viruses? 

There's various correlates that have been defined, but the best one really when we're thinking about universal flu vaccines is the induction of broadly neutralizing antibody responses, and what that means is that an antibody that can neutralize or prevent the infection of a lot of different influenza viruses. And so that raises the question of, well, how do you get a vaccine that induces those responses?

And that is really where my lab is doing a lot of work to understand what are the sort of vaccines that would be capable of doing this, for one. And the second is that one major challenge when we come to flu vaccination is the fact that we have pre-existing immunity. And what that means is that everybody in this room has seen flu before. We all have some level of immunity against that. And that previous immunity really dictates how we respond to future vaccines, infections, things of that nature. And so we can make a vaccine that in a naive system, so a person that's never seen flu before, induces gorgeous, broadly neutralizing antibody responses, but pre-existing immunity kind of throws a wrench into that, and it really changes the way that we respond. And we need to understand, A) how do you induce those responses? But B) how do you design vaccines that actually overcome our past responses and biases towards flu to generate this broadly protective immunity?

Thomas Flaig:

In a universal flu vaccine approach, what would be the duration of efficacy? So would you still need those annual shots even if it was a similar vaccine per se each year?

Jenna Guthmiller:

Yeah, so the goal is that it wouldn't be a yearly shot. Right? We would be hopefully looking at once every five to 10 years. So like a lot of standard vaccines, things like Tdap where they recommend every 10 years, that's really where we would like to see the flu field going.

That said, I am also not opposed to yearly vaccines, particularly to just boost immunity, particularly at mucosal sites. And one really nice thing about giving a vaccine up the nose is that it's pretty non-invasive. It doesn't require needles. It's just a little, if you ever use nasal sprays, it's basically just like that. And so that could also be a good way of boosting immune responses locally at the sites where we get infected. Doing that every year, I think, is probably a very feasible thing just for your routine doctor visit, just get a little puff in the nose.

Chris Casey:

Well, I can see that could have huge advantages in terms of people participating in a vaccine if it was less of an ordeal, they have to schedule, they have to get the shot, if they may not need needles.

What about do you foresee, and this brings up another vaccine that has been a specter in the last couple of years that we've all experienced, and that's the COVID vaccine - and how that's changing every year. Do you foresee a time where maybe there's a universal flu and a COVID vaccine made available together? Once again, just to simplify it from the patient's point of view.

Jenna Guthmiller:

Sure. So we'll take a step back to seasonal vaccines. So there's already a concerted effort by particularly Moderna to make combined flu and COVID vaccines. So basically just the same vaccine, one shot, you only have to go in once to get both vaccines. Right? So that's certainly a way to provide protection against seasonal viruses as best as possible.

But as far as a universal flu and COVID vaccine, what it's probably going to take to generate a universal flu vaccine is going to be different than what is required to make a universal COVID vaccine just because the diversity of SARS-CoV-2, or the virus that caused COVID, is not really at the same level as flu. As I mentioned, we got H1N1, we got H3N2, we got influenza B that we’ve got to tackle that co-circulate with each other, whereas something like SARS-CoV-2 is one virus. Yes, it's changing over time, but it really just has different requirements.

As far as let's say we can make vaccines against both, I think it's totally feasible to give them at the same time to generate that robust (response), but I don't think that we should be holding out for something that's going to be universal for both at the same time. If one becomes available before the other, we should certainly go out and get that.

Chris Casey:

you may have already touched on this, but what kind of vaccine technology are you studying for the universal vaccine? Is it the mRNA option?

Jenna Guthmiller:

Yeah, so my lab is less about platform, which mRNA would be what we would refer to as a vaccine platform. We're really more interested in the sort of antigens or immunogens, so thing that we give to somebody that's going to elicit an immune response. And we're really interested in trying to engineer those antigens to elicit more broadly protective immunity. And certainly then you can start, once you know that that's doing what you want it to do, you can start to go, "Well, what platform is going to do this the best?"

And certainly, mRNA is an easy way to do that in some ways. You just plop the sequence of that, that protein, onto an mRNA and then inject it into somebody and that's pretty efficient. But there's other ways that are better at inducing, in my biases, mucosal immune responses because we really want to provide better protection where we're getting infected, and mRNA is not going to be the way to do that. That's going to be much better at systemic immune responses, which are more correlated with providing protection against severe disease. But in order to prevent influenza as a disease altogether, you really need to have robust mucosal immunity within your nose, essentially. And there's other platforms that are better at doing that, like the live attenuated influenza virus, as I mentioned.

Thomas Flaig:

We started out by talking about influenza, avian and seasonal and so forth. And it's, I think, important to consider the impact of influenza on human health and the healthcare system. In a typical year, it can have a significant impact, and those less common, but very serious flu pandemic situations are dramatic. So any comment about just the impact of influenza on human health and public health?

Jenna Guthmiller:

Yeah, I mean, I think influenza viruses, and you can probably speak better to this than I can, continues to be a drag on healthcare systems when the flu season begins. And this is a big issue, and certainly, hospital wards get overwhelmed with flu cases, and now adding onto that SARS-CoV-2, RSV, all of these viruses that like to circulate at the same time have a major burden. And if we can potentially take out one or two of these as a human disease, that certainly makes getting your routine treatment for other things much more accessible when the healthcare system just isn't so strained.

Thomas Flaig:

I mean, the strain is the seasonality of it, right?

Jenna Guthmiller:

Yeah.

You think we'd be better able to predict it at this point, right, that it's just going to happen every year at the same time.

Thomas Flaig:

Hospitals are pretty busy places year round, so then if you have a seasonal influx of whatever virus is floating around, it can even have a major impact.

And just in your historical perspective or however you want to talk about it, pandemics, influenza pandemics and how... We've been thinking about COVID the last few years, but just in general, what's been the history of influenza pandemics? How frequently? How severe? When was our last one?

Jenna Guthmiller:

Yeah. So I think if you were to ask any sort of emerging virus expert on December 30th, 2019, "What would be the virus that would cause the next pandemic?" they would've told you it's an influenza virus. Just for reference, I think the first report of COVID-19 was really made worldwide December 31st, 2019. So just for reference, really nobody saw that a coronavirus was going to be the next pandemic. So influenza viruses historically have caused them.

In a span from 1918 to 2009, we had four influenza pandemics. I think most famous of those is the 1918, referred to as the Spanish flu. We can certainly go into the history as to why it's called the Spanish Flu because it's fascinating. But that virus, if you look at the average lifespan of a person, there's a noticeable dip that happens around 1918 and that is because of the 1918 Spanish Flu. It just had a massive impact. 50 million people projected to have died of that.

And in fact, as I mentioned before, the US military's been very involved in making flu vaccines. Part of that reason is just readiness of our military, but also because as many people died of the 1918 flu during World War I than died on the battlefield. So really huge implications for military readiness if a pandemic occurs, and having better vaccines that can provide protection is certainly good for wartime, if you will.

Chris Casey:

And as far as the flu goes, you hear about it especially impacting older people every year, being the most vulnerable. But what about children? Are they pretty vulnerable as well to the influenza virus?

Jenna Guthmiller:

Children, particularly infants and toddlers, are the most susceptible to influenza infections, in part because they have no immunity against the virus, so this is the first exposure to the virus. And anywhere from about 100 to 200 kids die in the US every year from influenza. So it's not an insignificant cause of death in that age group.

Chris Casey:

And do you feel like there's... You talked about the history of flu pandemics over the last 100 years. Do you have any sense on the likelihood of the threat of another flu pandemic hitting us?

Jenna Guthmiller:

Yeah, I mean, it's very concerning, as a person that studies flu, seeing the current H5N1 outbreak. Hopefully, you guys were a little bit alarmed to learn that there's been 40-plus infections just this year.

Thomas Flaig:

Those are human infections, right? Yeah.

Jenna Guthmiller:

Human infections of H5N1 in the US this year alone.

Thomas Flaig:

Documented cases?

Jenna Guthmiller:

And actually, the majority of those, the last 30 of them have essentially been in the last month to two months, so we're seeing more. And I think that's an aspect of we're looking more so I think they've been occurring for a while.

But secondarily to that, when this was first identified in dairy cows and then people, dairy farm workers, we were at the tail end of the flu season. And as we talk about things like antigenic shift, this outbreak doesn't seem to be going anywhere. Utah just got added to the list of states that's being affected by the dairy cow outbreak. We're going into the human flu season. You can imagine that if you are a dairy farm worker that's being exposed to human seasonal flu viruses in your daily life as just engaging with other humans, and then also potentially working with a dairy cow that's infected, that sets us up for what, again, is referred to as that antigenic shift.

So as a person studying flu, that is very concerning, and I think we really need to keep a close eye on what is going on with the H5N1 outbreak.

Chris Casey:

Just going back to the public service announcement aspect of things and people entering the flu season, could you explain, Jenna, just what are a few tips people can follow just in their daily routine to best avoid getting the flu this year? And perhaps, I suppose, starting with a vaccination?

Jenna Guthmiller:

Yeah, so I mean, that's what I was going to say. So the first thing you can do is get vaccinated. Certainly that is the most effective way to prevent yourself from getting the flu. But secondarily, as far as in daily life, washing your hands, trying to stay away from sick people as best you can. So if somebody in your family is saying they're ill, do a little brief quarantine, try to keep distance from them, try not to be in the same space for extended periods of time. And then similarly, if you do get infected, also do the people around you a courtesy of not going out into the world and spreading that. So if you are sick, please wear a mask to prevent the spread of flu.

Thomas Flaig:

I think one of the things that came out of COVID is this idea, if you're sick, you don't have to go to work. And I think that's been one change in the way people operate. Five years ago, you'd tough it out and you'd go to work when you're still (sick). And I think there's more acceptance to saying, "I'm sick, I'm going to stay home" when you can. And I think that's, getting your flu shot and then being thoughtful when you are sick of trying to isolate yourself in a general sense, I think that's one of the things that's come out of COVID in some ways.

Jenna Guthmiller:

Yeah. And I think nobody ever wants to hear this, but oftentimes the factor that starts the flu season is the holidays, right? And if you are feeling ill during the holidays, it's not a bad idea to not go because oftentimes it will be people of varying ages that are more or less susceptible to infection and that particularly kids, because kids will just go to school, they'll spread it amongst themselves, their teachers, their parents, and if you are sick during the holiday season, maybe take a beat and stay home. Even though that may be sad, at the end of the day, you could be the difference between somebody getting critically ill and not.

Chris Casey:

Well, this conversation has been fascinating and infectious disease is a very interesting topic, and we could go on about this all day, but all of us have to somehow get through the treacherous snow conditions to get home later today so we should probably start to wrap things up.

So Jenna, I would just like to say thank you for joining us and sharing all your expertise and kudos on your lab and your team's work toward the universal flu vaccine. I think that that's a highly exciting development on the horizon, and I applaud that you are delving deeply into that area.

Jenna Guthmiller:

Yeah, thank you.

Thomas Flaig:

Yeah, great to learn more about your work and thanks for all you're doing in this important area.

Jenna Guthmiller:

Yeah, thank you. Thanks for having me.

Thomas Flaig:

Thank you.