- The U.S. government has two candidate vaccine viruses for H5N1 bird flu that could be used to make vaccines.
- Studies suggest vaccines based on these would offer good protection against the bird flu virus circulating among cattle in the U.S.
- It would take months to produce and ship millions of doses, but experts worry that uptake will still be low.
The H5N1 bird flu circulating in the U.S. remains far more dangerous for birds than for people.
Currently, this strain of the flu that circulated in cows has led to just a single person being affected in the last few months. But the strain of influenza has the potential to mutate, so federal health officials are already thinking ahead toward a potential vaccine.
The country has two candidate vaccine viruses available to manufacturers for the production of a bird flu vaccine, the Centers for Disease Control and Prevention (CDC) said on its website.
How U.S. could make millions of bird flu vaccines within weeks
“These [candidate vaccine viruses] are like seed stock that are kept in reserve in case there is an outbreak of that particular strain,” said David Diemert, MD, a professor of medicine in the School of Medicine and Health Sciences at George Washington University, and director of the GW Vaccine Research Unit.
If bird flu started easily spreading to people, “[the candidate vaccine virus] can be sent to manufacturers to make millions of doses of vaccine,” he said, “using the existing hen egg technology that we normally use for the regular seasonal vaccine.”
A candidate vaccine virus is attenuated, or weakened version of the virus. As a result, it is unlikely to lead to active infections in people who get the vaccine.
This type of weakened virus is able to grow well in hen eggs, which is what most manufacturers use to produce seasonal flu vaccine.
The candidate vaccine would also have the surface proteins — known as hemagglutinin — of the virus circulating in the community. This enables a vaccine to generate a protective immune response.
Would these bird flu vaccines work?
The U.S. National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) has four types of H5N1 candidate vaccine viruses, reported STAT News. The bird flu affecting dairy cows is a strain of H5N1.
Only two of these candidate vaccine viruses are a good match for the currently circulating strain of bird flu.
Studies suggest that vaccines based on these two candidate vaccine viruses “will offer good cross-protection against cattle outbreak viruses,” Demetre Daskalakis, director of the National Center for Immunization and Respiratory Diseases, said on a call on May 1.
However, Amesh Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security at the Bloomberg School of Public Health, cautioned that the candidate vaccine viruses are not a “perfect match” for the currently circulating strain of H5N1. This means they may not produce vaccines very effective at preventing disease.
In addition, research done in the mid-2000s found that H5N1 vaccines don’t trigger a strong immune response in people unless it is given in a large enough dose; or if it is given with a compound known as an adjuvant, which boosts the immune response.
Adalja pointed out that the H5N1 vaccines that we have in the stockpile are really not that good at provoking an immune response.
“Even for the viruses they are targeted against,” said Adalja. “In clinical trials, the protective antibody levels that people had were modest.”
One of these existing H5N1 vaccines in the NPIVS is made by CSL Seqirus, which supplies flu vaccine to the U.S. market.
Still, Diemert thinks a bird flu vaccine based on the two candidate vaccine viruses in the NPIVS would be effective and potentially more effective than seasonal influenza vaccines.
This is because a bird flu vaccine would likely only have to target a single virus strain.
In contrast, during seasonal flu season, there may be multiple strains of influenza that spread. Seasonal flu vaccines are developed to target certain strains of influenza every year. The vaccines are developed in the summer and early fall by looking at common strains in the Southern Hemisphere. But during flu season the strains that become more common in North America may not be the strains the vaccine was primed to target.
As a result, seasonal flu vaccines may end up targeting strains of influenza virus that are not the ones in circulation that year.
“That’s one of the reasons that [seasonal flu vaccines] are not 100% effective because they’re not a perfect match,” said Diemert.
Would vaccines need FDA approval?
Before bird flu vaccines could be rolled out, they would need to be approved by the Food and Drug Administration (FDA) but the agency has a process for approving updated seasonal flu vaccines each year.
So this should go fairly smoothly, said Diemert, “especially since the [bird flu] vaccines would be made using the same manufacturing process that they use every year [for seasonal flu vaccines].”
Also, “I’m sure if there was a massive outbreak of this particular strain, then the FDA would speed things up,” he said. “So I don’t see regulatory approval being a rate-limiting step.”
How quickly could the vaccine be rolled out?
In terms of getting the vaccine to the people who need it the most, “all of the pieces are in place to be able to roll out a vaccine relatively quickly,” said Diemert.
However, “when you send [the candidate vaccine virus] to the manufacturer, it still takes weeks to months to make all the doses you need,” he said.
This is especially difficult in a “fast-moving situation” such as a pandemic, said Peter Chin-Hong, MD, an infectious disease physician at UCSF Health.
Federal health officials estimate that over 100 million doses could be shipped within three to four months. However, they expect people to need two doses, so this would only cover 50 million people.
Vaccine production could also be affected by the same virus the vaccine would be designed to protect against.
Manufacturers most often use hen eggs to produce flu vaccines, but chickens are also susceptible to the bird flu virus that is affecting cattle.
So, “if you have a global [influenza] pandemic, and you have birds dying too, that may constrain supplies such as chicken eggs,” said Adalja.
As of May 6, over 5 million chickens and other commercial or backyard poultry birds in the United States have been affected by highly pathogenic avian influenza (HPAI). which includes H5N1, reports the U.S. Department of Agriculture.
The big question is whether enough vaccine doses could be rolled out in time to make a difference.
“With the 2009 H1N1 pandemic, by the time the vaccine came out, the pandemic had already dissipated,” said Chin-Hong.
During that outbreak, tens of millions of Americans were vaccinated, but by the time the vaccine doses were available, the fall wave had subsided.
However, “this is 2024 and things have changed,” said Chin-Hong, referring to the fast development and rollout of the COVID-19 vaccines. “When people put their mind to it, it could be done fast … But the devil is in the details.”
Overall, “it’s going to take some time to actually gear up to be able to vaccinate everybody who’s at risk for flu,” said Adalja. “And as I said, the candidate vaccine virus that is stockpiled is not a perfect match. And even if it were a perfect match, [the H5N1 vaccine] is not a great vaccine to begin with.”
mRNA vaccines and other options
Federal health officials said the government is also pursuing an mRNA bird flu vaccine, based on the same technology as Pfizer’s and Moderna’s COVID-19 vaccines.
Chin-Hong said this type of vaccine could potentially be updated more quickly to match the currently circulating strains of the virus. But these vaccines have their own challenges, he said, such as needing to be stored at extremely cold temperatures.
In addition, given that these vaccines would be a new use of the mRNA vaccine technology, the FDA may require clinical trials which could delay the roll-out to the greater population.
There are other options for dealing with an outbreak of bird flu in people, including antivirals such as Tamiflu, which would be given to people who are already infected.
“Different interventions speak to different people,” said Chin-Hong. “In general, Americans prefer to treat something rather than prevent it, which can be a challenge.”
Vaccine hesitancy may slow uptake
As seen during the COVID-19 pandemic, it’s not just how many vaccine doses you can ship that matters, but also how many people receive the vaccines.
“The problem we may have is that there is more vaccine hesitancy now, so people may not be as willing to get vaccinated,” said Diemert. “I don’t know if that will be different because the [hen egg] flu vaccine technology has been around for decades and there’s a lot of evidence of its safety.”
Chin-Hong pointed to the poor current COVID-19 vaccination rates among American adults as a sign of vaccine fatigue.
Around 22% of all American adults have received the updated COVID-19 vaccine, with a slightly better rate (38%) among older adults, according to the CDC. Both rates are much lower than health officials would like to see.
“That shows how fatigued people are [with vaccination campaigns],” said Chin-Hong. “This [hesitancy] would need to be addressed in the same breath as having a well-oiled plan [for rolling out the vaccines].”
Adalja is concerned not just about vaccine hesitancy, but with growing public opposition to vaccines, in general.
“In 2009 with H1N1, vaccination uptake was subpar because concerns raised by the anti-vaccine community — which were unwarranted concerns — dissuaded people from getting vaccinated,” he said.
But “after COVID-19, the anti-vaccine movement is more powerful than it has been in decades,” he added. “So I think mounting a vaccination campaign in an [future] emergency is going to be very difficult to do in the current political environment.”
Takeaway
There is no sign that the H5N1 bird flu circulating in dairy cow herds is developing the ability to spread easily to people. But federal health officials are planning for the rollout of a bird flu vaccine as a precaution.
The federal government has two candidate vaccine viruses stockpiled. These are weakened so they cannot infect people or cause illness, but they grow well in hen eggs, which is how flu vaccine are most often made.
The candidate vaccine viruses are not a “perfect match” for the bird flu virus currently circulating, but they should offer good protection, say health officials. However, experts are concerned that vaccine fatigue will deter uptake.
