Would a Seasonal Flu Vaccine Protect You Against H5N1 Bird Flu at All?

It's worth a shot.

Photo by Markus Spiske on Unsplash

As an H5N1 pandemic looms over us, the CDC is strongly recommending flu shots while urging farmworkers to get vaccinated. This year’s shot is trivalent, meaning it contains vital proteins from Flu A strains H1N1, H3N2, and one Flu B virus. In the past, they’ve used a quadrivalent vaccine, but this year they excluded a Flu B strain they believe to have been essentially eradicated (because of enhanced protection measures like masking and clean air). All of this made me wonder how well a seasonal flu vaccine protects against a novel strain. The CDC’s official answer is that it doesn’t. However, there’s a big but they won’t say…

Studies suggest otherwise.

Normally, your immune system only develops a memory of specific antigens. Your immunity to one virus doesn’t transfer to others. However, in the case of flu viruses, cross-protection can happen. In fact, recent research covered in Nature stresses the need for universal flu vaccines that generate mucosal immunity, which could provide protection against a range of strains, even H5N1.

We have the technology to do this. We could already have universal flu vaccines by now if our governments had invested in them.

They didn’t, not really.

Most of us have probably never thought to learn about the different types of flu vaccine on the market. Turns out, there’s a difference. For example, one popular brand this year is Flublok, which claims to offer three times the standard antigen dose and provides 30 percent better protection in clinical studies. During a given season, you can choose between nine different flu shots. Some of them offer an adjuvant, like Novavax does for the other killer disease. It’s usually available for adults 65 and older. Higher dose adjuvanted vaccines could benefit many of us this year, and it would be nice if public health officials were more forthcoming about that.

Several studies indicate that a seasonal flu vaccine can offer partial protection against H5N1 specifically, even against death.

Let’s get into them.

A study in a 2008 issue of Emerging Infectious Diseases found that a seasonal flu vaccine can provide partial protection against H5N1. Researchers looked for CD4 cells specific to the H5N1 strain in participants, and they found that a regular flu vaccine “enhanced the frequency of such reactive CD4 T cells.” As they go on, “We also observed that seasonal vaccine is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors.”

So getting a seasonal flu vaccine can help you produce antibodies and CD4 cells to fight H5N1, even if it doesn’t stop infection. These antibodies can “reduce virus replication and spread.” They speculate that it happens because your immune system still recognizes the N1 neuraminidase proteins, even if the H1 hemagglutinin protein changes. The vast majority of flu viruses we’ve dealt with as humans are H1, H2, or H3, meaning they have the H1-3 hemagglutinin protein.

We’ve never been threatened with an H5 flu virus except in rare moments like the 1997 Hong Kong outbreak. That’s part of what makes the sudden evolution of H5N1 so alarming and unpredictable to scientists.

It wasn’t supposed to happen.

As the 2008 Emerging Infectious Diseases authors go on to say, “adults living in the United States who were never exposed to H5N1… have shown cross-type cellular immunity to influenza A virus strains derived from swine and avian species,” including H5N1. In other words, previous flu infections and vaccinations seem to give you a layer of defense.

Several studies have found that vaccination or infection with other flu strains provide a layer of defense against H5N1. A 2001 study in the Journal of Virology confirms that H9N2 flu was circulating among chickens in Hong Kong before the 1997 H5N1 outbreak. Apparently, a “cross-reactive cellular immune response induced by influenza (H9N2) was able to protect chickens from H5N1.” Their T lymphocytes and CD8 T cells “recognized target cells infected with either an H5N1 or H9N2 influenza virus.” Their study found that chickens with a previous H9N2 infection survived H5N1, but they still contracted the virus and shed it in their poop. It was good news for the chickens, but bad news for the people who ate them, because there was no obvious way to know they were infected.

Another 2007 study in PLOS Medicine found that vaccinating mice against H1N1 flu “partially protected” them “from lethal challenge with H5N1 virus” as well as other avian flu recombinants. They also managed to successfully transfer antibodies from vaccinated mice to unvaccinated ones. They concluded that “a portion of the human population could have some degree of resistance to H5N1 influenza, with the possibility that this could be induced or enhanced through immunization with seasonal influenza vaccines.”

Another 2013 study in the Journal of Virology on ferrets found that “vaccination with seasonal influenza vaccine afforded partial protection against lethal H5N1 challenge and shows that use of either AIPO4 or Iscomatrix adjuvant with the vaccine resulted in complete protection against disease and death.” Again, the antibodies targeting the N1 neuraminidase protein does most of the heavy lifting by inhibiting reproduction of that specific protein. As they conclude, “adjuvanted seasonal trivalent vaccine could be used as an interim measure to decrease morbidity and mortality from H5N1 prior to the availability of a specific vaccine.”

A 2018 study in Frontiers in Immunology also reviews the case for cross-protection against flu viruses. They discuss several studies that found varying levels of cross-protection between flu infections and vaccinations. They point to a 2009 study in Vaccine that found vaccinating mice with H3N2 flu virus four weeks prior provided “protective immunity” against H5N1. So, it’s a good thing that the flu vaccine contains H1N1 as well as H3N2. If you’re looking for cross-protection against H5N1 bird flu, that looks like the way to go.

On a basic level, all of this gives us a little relief.

All of this information directly contradicts statements by the CDC this year that the general public has little or no existing immunity to H5N1. Roughly 40-50 percent of adults in the U.S. get their flu shot.

It doesn’t make much sense…

This does:

According to medical lore surrounding the 1918 flu, older adults didn’t die or get as sick because their immune systems remembered the Russian flu of 1890, and that gave them protection. As a study in PLoS One explains, that’s partially true. There’s actually four prevailing theories about why young, healthy adults died in such large numbers. First, it’s true that younger adults had never been exposed to anything quite like the H1N1 flu virus. Second, soldiers were also fighting off a range of other diseases like tuberculosis and measles, which weakened them. Third, healthy adults mounted an immune response that was too strong, killing them. Fourth, and counterintuitively, adults around the age of 28 in particular had the worst mortality because they did catch the 1890 Russian flu, but they caught it too soon. The 1890 flu imprinted on their immune systems and generated a dysregulated response to the 1918 flu. This would be a case of “antigenic sin.”

If you get your flu shot this year, it could help protect you from death via H5N1. Given the absence of alternatives, I’ll take it. If our governments were serious, they would be making us all eligible for high-dose, adjuvanted flu vaccines. Those seem to offer the greatest chance for cross-protection.

The irony is that if we were facing “the wrong strain” of bird flu, then getting a seasonal flu vaccine could make things worse.

Fortunately, we’re not in that situation.

Now, let’s get to the fun part.

You might’ve noticed a little uptick in messaging from public health agencies lately, stressing the importance of getting your flu vaccine, while downplaying or even completely neglecting to mention Covid.

This could explain why.

Not to get all conspiratorial on you, but it’s pretty clear from multiple reports over the last year that we’re speeding headfirst into an H5N1 pandemic. All of our public health agencies from the USDA to the CDC have dropped the ball, rolling right over for the dairy and cattle industries who often refused to cooperate with testing or even giving their workers adequate PPE. If we’re going to be completely honest, it was always a long shot to try to stop H5N1 from spreading in cattle when we know this virus has been burning through wild animal populations in ways the world has never seen. It was a matter of time before human spillover.

Our vaccine options are… limited.

Several governments have bird flu vaccine stockpiled, but they don’t know exactly how well it would stand up against a real pandemic. Studies have indicated that vaccines targeting earlier clades of H5N1 would do okay “in a pinch.” The U.S. has ordered 4.8 million doses of newer vaccines. They’ve also contracted with Moderna to produce an mRNA bird flu formula. All combined, they plan to have just barely 10 million doses by the spring of 2025.

It won’t be enough.

They know that.

The U.S. government has also been urging farmworkers to get a flu vaccine for a mishmash of reasons, and even paying for the shots. (Mine was $100). The reason they cite most often is trying to prevent bird flu from recombining with an existing flu. Based on the studies we’ve seen, I think they know it also affords them a little cushion to continue claiming H5N1 is mild. Based on the studies reviewed here, if you got vaccinated with flu, and you got treated in time, then you have decent odds against an H5N1 infection, contrary to the horrors we’ve anticipated.

At least one clinic has developed a pan-flu vaccine that works against multiple strains of flu, including avian flu. It doesn’t look like our governments are pouring any money into those, instead focusing on vaccines that target only one or a handful of strains. Yeah, that’s disappointing.

Behind closed doors, public health officials seem to know that we should be doing a lot more to prepare for a bird flu pandemic, but they don’t want to risk the political backlash during election season. That means it’s up to us to be smart and do as much as we can to protect ourselves and each other.

It’s worth remembering that the first flu vaccines didn’t become available until the 1940s, thanks to the work of Thomas Francis and Jonas Salk. So young adults in 1918 truly had no immune preparation whatsoever. Minimizers have abused the idea of cross-protection and herd immunity in order to justify a lack of vigilance against disease. In truth, cross-protection can happen sometimes. When it does, we should take advantage of it and add that to our list of other mitigations, including quality masks like N95s and clean air.

Will a seasonal flu vaccine protect you against H5N1?

It’s worth a shot.