It’s flu season: What’s in the shot? Should we be worried about avian influenza? And the promise of a universal vaccine

Tiny Matters

Why do we need an influenza vaccine every year when there are many vaccines we only need to get once every few decades? In this episode, Deboki and Sam kick things off by covering the different strains of influenza that are most likely to cause, or already caused, pandemics. They also chat with experts about the new, more deadly strain of avian influenza — H5N1 — that has been making its rounds in the United States since January 2022, leading to the deaths of over 58 million birds, not just impacting farms and egg prices but wild bird populations.

Transcript of this Episode

Sam Jones: It’s almost October, which means leaves are changing, Halloween is right around the corner and… it’s flu season. Again. That means it’s time to be on the lookout for all those familiar flu symptoms: fever, cough, headache, muscle and joint pain, and a runny nose.

Deboki Chakravarti: The majority of people recover from the flu within a week, but it can be incredibly dangerous for some people. And flu viruses circulate across the globe, which leads to 3 to 5 million cases of severe illness, and hundreds of thousands of deaths every year.

And flu season also means that every year, around this time, we’re told the same thing: go get your flu shot.

Welcome to Tiny Matters, I’m Deboki Chakravarti and I’m joined by my co-host Sam Jones.

Sam Jones: In today’s episode, Deboki and I will get into how the annual flu shot works and why we are told to get jabbed with it every year when there are plenty of vaccines that we get once, maybe twice, throughout our entire lifetimes. We’ll also discuss influenza viruses more broadly.

I would bet that many of you saw headlines about avian flu over the last year or so or, at the very least, saw egg prices skyrocket as a result. Avian flu, swine flu, the flu viruses that impact us humans — they're all under a massive influenza umbrella.
Deboki: There are four types of influenza viruses: A, B, C, and D.

Influenza viruses A and B cause seasonal epidemics every year. But only influenza A viruses are known to cause pandemics, meaning they don’t stick within a region or country, they spread across the globe. Influenza C viruses cause mild illness and aren’t believed to cause human epidemics. And influenza D viruses mostly impact cattle but can spill over into other animals, though they’re not known to make people sick.

Sam: Because influenza type A viruses are known to cause pandemics, they’ll be the focus of this episode. So type A influenza viruses have two types of antigens or proteins that stick off of their surface: Hemagglutinin and neuraminidase. These antigens are what trigger your body’s immune response.

But to complicate things, there are 18 different versions or subtypes of hemagglutinin and 11 of neuraminidase. And those subtypes can combine in different ways. You’ve probably heard of at least a couple of these, including hemagglutinin 1 neuraminidase 1, better known as H1N1.   

Deboki: You might know H1N1 even better as swine flu, which has caused a number of pandemics and epidemics. In 2009, a new strain of H1N1 quickly spread across the globe and was labeled a pandemic by the World Health Organization. But it’s probably even more notorious for causing the 1918 influenza pandemic, one of the deadliest pandemics in human history. During the 1918 pandemic, H1N1 infected about 500 million people around the world, and caused the deaths of somewhere between 50 to 100 million people.

And actually, for decades leading up to COVID-19, scientists expected the next big pandemic to be caused by an influenza virus, not a coronavirus.

Sam: Why flu? Well, for a number of reasons. First, there are so many different strains of influenza. Well over 100 of influenza A alone. Influenza viruses also rapidly mutate and are well known to jump into humans from other species, like birds. Over the last couple of years, a new strain of avian influenza H5N1 has been circulating in birds and is considered highly pathogenic or ‘high path.’

Karen Grogan: Those are viruses that cause acute mortality. You may see no clinical signs, meaning you just may see acute death because the virus is so pathogenic. This is the version that we've had circulating over the past two years in North America and globally, actually Europe has had the same instances.

Sam: That’s Karen Grogan, clinical associate professor of avian medicine at the University of Georgia College of Veterinary Medicine, with the Poultry Diagnostic and Research Center.

Karen Grogan: And then we also have viruses that circulate that are called low pathogenic viruses. They can cause a variety of clinical signs from basically an upper respiratory infection, like a cold sort of congestion in the birds. It can cause gastrointestinal signs, intestinal upset. And we can also see reproduction issues. So if it gets into egg laying birds, they will drop in egg production, but they'll tend to come back. The concern is that as those low pathogenic viruses circulate in a population, avian influenza viruses are very adept at mutating.

So the longer those low path viruses are allowed to circulate, they can develop pathogenicity. In the United States, we have a low-path avian influenza surveillance program that is constantly going on so that we know what's going on in commercial poultry. And then when we have these highly pathogenic viruses, that's when the federal government comes in, our partners at USDA, and we want to stop that virus.

Deboki: Starting in January, 2022, a highly pathogenic strain of H5N1 was detected in U.S. commercial poultry, wild aquatic birds, and backyard flocks that people use to get eggs for themselves or to sell locally, but not necessarily to sell on a large scale.

It was the first detection of H5N1 in the U.S. since 2016. As of August, 2023, over 58 million birds have been affected. The good news is that the last commercial detection was in April of 2023 and there have been just a few detections in backyard flocks since.

This H5N1 outbreak made headlines in part because egg prices tripled or even quadruped, but also because there was a noticeable impact on wild birds.

Karen Grogan: I think in our quick information age, videos of dying snow geese or pelicans in South America… the impact on wild bird populations has been unique for this virus. In previous viruses, they would circulate in wild birds and not really cause a lot of mortality. These viruses are known to circulate in wild waterfowl, and they just shed a lot of the virus, but they don't necessarily die themselves. They're kind of considered carriers. So then the virus is in the environment, and it carries into commercial poultry in that low path form. And then we always thought it mutates to the high path version once it's in commercial birds, in chickens or turkeys or quail.

This virus has been unique in that it is in its high pathogenic form in wild birds. So we have seen major impacts in terms of bald eagle populations. They had nest failures that we've documented. There's research that came out of the University of Georgia, from my colleagues at the Southeastern Cooperative Wildlife Diseases Study. I guess the breeding pair was affected and then the nest would fail, which is very impactful for a very valued species here. And the California condors were majorly impacted when they became infected.

Deboki: So you might be wondering…if we can develop flu vaccines for humans, couldn’t we also make flu vaccines for birds? And yes, we can. In May of this year, the USDA began testing the efficacy of a handful of vaccines against the current highly pathogenic strain of H5N1.

But Karen told us that there are a few things keeping bird vaccinations from becoming a regular prevention strategy. For one, you have to actually get the vaccination to the birds, which means giving shots to millions of birds…that’s a lot of birds! And a massive logistical hurdle!

Another major issue is trade, particularly if another country is concerned about the vaccine itself and decides to impose trade restrictions.

Sam: Karen told us that the best use of a vaccine would be a targeted approach in small populations, like animals in zoos or endangered species.

Karen Grogan: And maybe it's not necessary or feasible in the commercial setting because we do a lot of protection of our flocks through what's called biosecurity, meaning we don't allow visitors onto the farm. If you come onto the farm, you're washing your vehicle, you are spraying down your tires, you're gonna take a shower, you're gonna put on different clothes, you're changing your shoes. So we protect our commercial flocks that way. But those other small operations or backyard flocks, zoos or a very important endangered species like the California condor, those would be potential ways we could see vaccine use moving forward.

Sam: And although this strain of avian influenza has been extremely destructive to birds, only one case has been reported of a person being infected, and it was someone who worked in a live bird market.

Karen Grogan: We have, in years past, had what were originally avian influenza viruses also circulate in people. This particular one that we are dealing with now has not done that.

But on the whole, if you look, from a public health context, influenza is considered a zoonotic disease, meaning that it can pass from animals to people. And we do want to be concerned about it. So in terms of the poultry industry, we require that our workers are vaccinated with the human flu vaccines. And what that allows is if somehow it were to make a jump that then you at least have some protection to what could potentially come out of the birds that you're working with.

Sam: The perfect segue, totally not planned at all… Let’s talk about the flu vaccine for us humans.

Deboki: The annual flu vaccine contains inactivated influenza virus, meaning it can’t infect you and get you sick with the flu when it’s in your body. It’s there to essentially trick your immune system into thinking your body’s under attack by the actual flu virus so that it fights it off and builds immunity.

Every flu season features a different set of strains circulating around the population. So the vaccines we’re given contain multiple strains of that inactive flu virus.

And we should mention that this is not the same design as the mRNA vaccines we’ve been hearing about so much over the last few years, that protect us from COVID-19. Those vaccines are packed with, well, messenger RNA or mRNA, not deactivated virus. That mRNA contains instructions for our cells to make protein, like the spike proteins that cover the COVID virus. And once those spike proteins are made, our immune system responds.

Sam: So, to quickly summarize: with the flu vaccine, our body is presented with an inactive virus covered in proteins that cause an immune response, helping us build protective immunity.

With the COVID vaccine, there’s one extra step: our body is presented with mRNA, our own cells translate that mRNA into proteins that cause an immune response, helping us build protective immunity.

Deboki: The flu vaccine, like any vaccine, is there to protect us. But it still is not my favorite thing to have to get it every year. To get a better understanding of why we need an annual flu shot, we reached out to Bali Pulendran, who is a Professor of Pathology and of Microbiology and Immunology at Stanford School of Medicine.

Sam with Bali Pulendran: We're advised every year that we should probably get the influenza vaccine. Yet, you know, with vaccines for things like polio, a lot of us, we got them as babies, and some people maybe don't get it again, or they wait 20, 30 years. And if they're traveling to a place where there has been a polio outbreak, they're advised to get the polio vaccine again, but that’s a huge difference, right? And so I'm wondering, is the main reason that we're told to get the influenza vaccine every year because there are so many influenza viruses circulating, whereas polio is consistently polio, and it seems like the mutation rate is very, very low, or is there other stuff going on too?

Bali Pulendran: Indeed the main reason why we have to get an annual flu shot is because of the circulating strains that differ from year to year. So this is why I think every year the manufacturers make a new flu vaccine, ideally, that contains the strains that are predicted to be circulating in that particular year. Now you mentioned polio. Polio, as you rightly say, is a virus that doesn't change nearly as often as influenza viruses do, and therefore you don't really need to get an annual booster shot. The other reason is that with the influenza vaccine the durability of the immune response is really not very long. Typically antibody responses to the influenza vaccine really wane with time. Estimates vary, but, you know, people think that these might decay very quickly within a few months of vaccination.

Sam with Bali Pulendran: That's really helpful, thank you. Something that you mentioned that I definitely wanna talk about is predicting which influenza strains are going to be the ones that we need a vaccine against each year. What goes into that prediction?

Bali Pulendran: The World Health Organization has set up these influenza monitoring centers throughout the world that's comprised of leading experts in the field of influenza, clinicians and scientists.

And they rely on health authorities throughout the world to send them data on what are the circulating strains of flu viruses in a given community. And so they pour through all of this data, they meet twice a year, they analyze all this data and make a recommendation to the vaccine manufacturers as to what strains they think should be included in the upcoming flu season. And based on that recommendation, the vaccine manufacturers then design the next season's flu vaccine.

Deboki: Bali told us that most of the time, the experts get it right — the recommendations they make match the actual strain that shows up in flu season. And you know it’s a good match if vaccinated people get sick with the flu in lower numbers compared to those who didn’t get vaccinated. Bali told us that a good year means around 70 - 80% of people who are vaccinated don’t get sick. But there can be years where the prediction is off.

Bali Pulendran: And this was most apparent, for example, in the 2014, 2015 flu season in which there wasn't really a good match. And so the efficacy of the vaccine was really quite low. It was about 10% or so. So that's the current approach in terms of anticipating what strains are likely to be circulating in the coming season, and then adapting the vaccine manufacturing strategy to include these strains.

Deboki: Bali and his lab work on a number of projects related to immunology and vaccination. One of those things is a universal vaccine. Not a universal flu vaccine — which maybe you’ve heard of and which we will talk about in just a minute — but a universal vaccine.

Bali Pulendran: Now, you know that vaccines are made against any given virus or any given pathogen, that's why we have a vaccine that is designed for COVID or another vaccine that's designed for flu. And that's how vaccines have been made for the last couple of hundred years. But what we're working on is a new concept called the universal vaccine. We want to design a vaccine that can protect against any virus or any pathogen. Listeners might be wondering, how on earth is that possible? Well, it turns out that a major aspect of our immune system is what we call the innate immune system.

Deboki: What we’ve been talking about in the episode up until this point is the adaptive immune system, where your immune system is trained to fight off a specific pathogen. Innate immunity, what Bali just mentioned, is your body's first line of defense against all viruses, bacteria and other pathogens that try to infect you. Your innate immune system doesn’t recognize what they are, it just sounds a general alarm.

Bali Pulendran: And what we're working on is a universal vaccine that would do exactly this, that could stimulate the innate immune system and launch this broad response. Now, the limitation of this is that unlike the adaptive immune system, which can last for years, this universal vaccine can last at most for months. You might be wondering, well, if it only lasts for a few months, then what's the point? You know, ideally you want something that can last for years. Right? The point is: imagine the next pandemic. Imagine not COVID-19 but COVID-27. And imagine that the next virus that comes is much, much more virulent, much more deadly than this COVID. How long did it take for us to develop these COVID vaccines back in 2020? It took a year, didn’t it? And a year was under warp speed conditions. That's with all the money in the world, all the collaboration and cooperation in the world, all the goodwill of all the nations coming together.

Where I think a universal vaccine would come into play is to provide an immediate relief, immediate protection that could serve as a stop gap measure for a few months until such time as the conventional vaccines come available. And this universal vaccine could simply be a nasal spray that you go to your CVS pharmacy with a prescription for your doctor and say, um, I'd like three doses of this universal vaccine, and it protects you for a few weeks or a few months. So that is the concept that we're working on, and we've got some exciting data on that.

Sam with Bali Pulendran: Of course you just spoke of a universal vaccine that would get a response from your innate immune system. But in thinking about influenza vaccines and other vaccines that are very specific to those viruses, we're talking about adaptive immunity, where do you see that technology going? Like, is everyone just gonna turn to mRNA vaccines? Would that help with our flu situation or not so much?

Bali Pulendran: I mean, I've been extraordinarily impressed by the efficacy and the power of the mRNA vaccine platform for several reasons. Firstly, they are clearly highly effective against protecting us from the COVID strains or variants. Secondly, just the rapidity with which we were able to make those mRNA vaccines is really my hats off to the vaccine manufacturers and vaccine developers. So I see an incredibly bright future for the mRNA vaccines, not just against COVID, but against influenza and RSV and many other global pandemics like malaria and TB and so on and so forth. But is that the only future of vaccines? Are they going to completely supplant the current technologies or technologies that have been available to us for the past several decades? I certainly do not think that that is the case.

Deboki: We’ve only discussed two general types of vaccines—mRNA and inactivated—but there are others out there. And Bali says that there are still questions about how long immunity lasts, or the extent to which different immune cells respond, depending on the type of vaccine. Which means that having options is a good thing. It will lead to the best vaccines possible and maybe even vaccines that don’t exist yet, like the universal flu vaccine.

Bali Pulendran: There's a major effort amongst different laboratories throughout the world to design what they call a universal influenza vaccine. This would be a vaccine that can protect against many, many different strains, if not most of the strains of influenza, including the pandemic strain. Now, there are several approaches being taken.

Deboki: One approach is to design a universal flu vaccine that includes antigen proteins that are common between different flu virus strains. There are also efforts to create an mRNA vaccine that might be able to protect us from way more strains of flu…right now, vaccines protect us from 3 or 4, but what if that number could go up to 20, 30, 40? Or maybe even include avian flu?

Sam with Karen Grogan: So my last question for you is really, if there's the potential for there to be a vaccine that just covers all of the flu’s, and so it would protect birds, it would protect people.

Karen Grogan: That is, I think, for most influenza researchers, that is their goal… the technology has developed so quickly. In 20 years, we have gone from having to re-isolate these viruses in embryos, and it would take you a long time to identify that that's what was causing it. And now we can run a real time PCR test in a number of hours and you know, okay, this is avian influenza in this flock.

The technology is there, hopefully we're moving in that direction. That would be a dream.

Deboki: So if you’re dragging your feet on getting your flu shot this year, here’s a few things to keep in mind. Influenza viruses are tricky. There are so many, in so many different species, and they are constantly mutating. And while there have been a few times where the flu virus prediction for the year is way off, it doesn’t happen often. So getting a flu shot should help protect you.

And each time you get your shot, you’re a little part of the exciting world of vaccine development. We’ve already reaped the benefits of advances in mRNA vaccines to rapidly deal with the COVID pandemic. And all that work scientists are doing to develop universal flu vaccines and universal vaccines is going to teach us more about how we can approach, and hopefully prevent, the next pandemic.

Sam: I can't remember who would be going for show and tell. I can totally go first. So there was a really brief news story that came out in Science Magazine back in May, and it's something that I've actually been thinking about a bit because, spoiler alert, I'm starting to work on an episode related to environmental DNA and trace DNA. For those of you who don't have experience in a lab or in doing this type of work, a lot of times, to actually do a lot of experiments, you are sending off requests for DNA to be sent to you, sent to the lab. Typically, in the past, this is something you would... There are a bunch of companies that do this, so you fill out what you need online and essentially you get a little DNA delivery.

Now, there are benchtop machines that can print DNA in the lab, so scientists don't need to necessarily order sequences from a synthetic biology company. Companies are not mandated, but expected to screen for potential bioterrorism in the requests that are made. But now if you have benchtop machines that can print DNA, now there isn't that additional layer of screening if a lab or a person somewhere has a benchtop machine that can print DNA. There was this report that went out in May that was done by a Washington DC think tank where they were warning that this is something that the government needs to be paying attention to because there is this added risk now that people can do this on their own. Current machines, they can synthesize somewhere around 200 base pairs. So base pairs and DNA, you got the ATCG, so you have machines that can actually create a string of about 200 of those.

But then more of the concern is that over the next few years, those sequence lengths could increase to thousands of base pairs. That's about the genome of a lot of small viruses. It also is big enough to be the genome of other pathogens. So that's really it, not trying to freak people out, I just thought it was something, I hadn't even considered it.

Deboki: I also don't want to add to freaking people out, but I was thinking about it's very easy now to stitch together small pieces of DNA into something bigger, where even if it's currently only at 200 base pairs, it would be annoying, it would still be very time-consuming.

Sam: For people who don't have experience with this, essentially there are ways of taking a fragment of DNA and then building longer sequences of DNA in each direction, so essentially you can create a very long piece of DNA. Honestly, I didn't even think about it, about how companies were, not mandated, but asked to watch for sequences that could be indicative that someone is planning something or working on something that is really dangerous. So I guess that some of the safeguards that were recommended in this report that came out in May were making sure that the makers of benchtop synthesizers checked to make sure the people that were purchasing these machines were legitimate researchers, maybe even building in software that blocks the synthesis of risky sequences, which feels tricky. I could just see there being all these issues within other sequences.

Deboki: That was super interesting. It also reminds me so much of 3D printing and the use of 3D printing to make guns.

Sam: Similar to this, when I was first seeing 3D printing in a lab, I never thought, "Oh, someone will use this to create weapons." Of course, there's always people trying to create weapons from everything.

Deboki: Yeah. Well, this is actually a really good segue, I think, of sorts. This is in the category of me telling you all to read this article. I'm not talking about a specific science thing, but I just thought it was really interesting, and I originally picked it because it was related to stuff that we had talked about in our Q&A episode about ethics and gene editing and the use of CRISPR to edit human embryos.

So this is an article that just came out in the New Yorker called The Transformative Alarming Power of Gene Editing. It's written by Dana Goodyear, and she's basically writing about this whole thing that we were talking about, the ethics around CRISPR, around editing human embryos, what happened in China with He Jiankui and everything he did, going through a lot of details. So if that was something that we had talked about in our Q&A that you were intrigued by and wanted to learn more about, I highly recommend this article because I think it's both really good for understanding the specifics about what happened in that specific experiment, which probably should not have happened, and talking about the scientific issues at play, the ethical issues at play. But it's also looking more broadly around the ethics of doing gene editing in embryos and why it is such a complicated thing to think through and what the state of that sort of research is right now. I just found it a really, really interesting article, so that's why I would recommend it.

Sam: Cool. It's nice to know that there's a story that synthesizes so much of that information because I think it's something we've been hearing about a lot for years now, but in short snippets, and so I'm excited to read that. I feel like it'll help me wrap my head around this technology and the pros, cons, scary things that people are trying to do, and just provide that context, so thanks.

Deboki: Thanks for tuning in to this week’s episode of Tiny Matters, a production of the American Chemical Society. This week’s script was written by Sam, who is also our executive producer, and was edited by me and by Michael David. It was fact-checked by Michelle Boucher. The Tiny Matters theme and episode sound design are by Michael Simonelli and the Charts & Leisure team. Our artwork was created by Derek Bressler.

Sam: Thanks so much to Karen Grogan and Bali Pulendran. If you want to support the show and look really cool drinking your morning cup of coffee, tea, juice, whatever, we have left a link to our Tiny Matters coffee mug. You can find me on social at samjscience.

Deboki: And you can find me at okidokiboki. See you next time.