The worst bird flu outbreak in US history continues with strange new developments. Bird flu is now infecting cows, the FDA found viral genetic material in milk, and a second human was recently infected.

H5N1 — the strain of highly pathogenic avian influenza circulating — currently poses little threat to people as spillover from animals to humans is rare, as is human-to-human transmission. But the recent spillover from birds to cows has triggered new fears that the virus could potentially mutate and cause a deadly human pandemic.

In the past two years, more than 90 million poultry birds from 48 US states have died from the virus or were killed in an attempt to slow the spread of the disease. (Wild birds and some mammals including sea lions and cats have gotten sick, too.)

Historically, farmers and poultry producers have used three main strategies to slow the spread: kill entire flocks of chickens and turkeys at the earliest sign of infection, surveil the movement of the virus, and improve biosecurity measures. This approach, sometimes referred to as “stamping out,” has thus far failed to curb bird flu and has raised concerns around animal cruelty. But as the virus continues to spread among livestock animals such as cows, relying on mass culling may not be as tenable.

“This virus is not going away,” said Carol Cardona, a professor at the University of Minnesota’s College of Veterinary Medicine. “And I’m not sure how sustainable this approach that we’re using is.”

Given the record-shattering infection rates among poultry and the unprecedented recent spillover to a wide range of other species, some bird flu experts and wildlife researchers are calling for renewed efforts to develop, test, and deploy a vaccine for poultry and potentially other species. Short of triggering a human pandemic, continued spread of bird flu among livestock could further threaten national and global food security.

“The current virus is being spread by wild birds. It is evident that the biosecurity arrangements on some farms, especially chicken layer and turkey farms, are not sufficient to prevent all virus incursions,” said Leslie Sims, the director of the Asia Pacific Veterinary Information Services. “Vaccination, if used, would add an additional layer of protection.”

Effective bird flu vaccines for poultry have existed for years and are even used routinely in other countries. But, in stark contrast to the Covid-19 pandemic when new vaccines were rapidly developed and rolled out, the US has yet to adopt vaccination as a disease control strategy for bird flu. The US Department of Agriculture reported promising results from clinical trials of several vaccine candidates, but despite this breakthrough, a slew of logistical, political, and economic challenges might prohibit their use.

A brief history of bird flu vaccines

Avian influenza vaccines have long been used around the world with varying degrees of success. In some countries, such as Egypt and China where bird flu is enzootic (meaning it is consistently present in animals), vaccination is routine.

In China, several vaccines have been developed. One study found that vaccinating against H5 and H7 subtypes reduced the number of cases in poultry, but another study pointed out that China continues to suffer recurrent outbreaks while others have suggested that culling would be a more cost-effective strategy. In Egypt, vaccination efforts have largely been unsuccessful, in part because it is the only disease control method used in the country.

Last year, Mexico, Guatemala, and other countries hit hard by the ongoing epidemic also started vaccinating against H5N1. In late 2022, Mexico began vaccinating broiler chickens and other birds in high-risk zones; almost one year later, the government declared the country free of influenza before reporting an outbreak in one flock on a commercial farm about a month later.

Only in the past year did some Western countries begin focusing on vaccination. In March 2023, the Dutch government announced that it had developed two bird flu vaccines and that laboratory trials revealed those vaccines to be effective at preventing infection and disease transmission. Italy and the Netherlands are also testing vaccines. In October, the French government started vaccinating ducks for avian influenza and has since vaccinated more than 21 million. According to a press release from France’s Ministry of Agriculture and Food Sovereignty, there have been only 10 outbreaks since vaccination began compared to 315 outbreaks during the same time in the previous year. (The EU is dividing research among member states.)

“Vaccination has played a very important role in the prevention of avian influenza elsewhere,” Sims said, adding that widespread preventive vaccination has also been used successfully in Hong Kong since 2003. In both France and Hong Kong, “the decision was taken to vaccinate because existing strengthened measures based around biosecurity could not prevent all cases of infection,” Sims explained.

Scientific, economic, and logistical challenges of mass bird flu vaccination

The US government has at least considered vaccination before.

During the 2014-2015 bird flu outbreak when more than 50 million chickens and turkeys died or were culled, the USDA stockpiled a bird flu vaccine. However, those vaccines were not deployed; the epidemic was instead brought under control through the stamping-out approach.

Following that outbreak, the USDA developed policies and guidance regarding the use of bird flu vaccines. A 2016 policy brief stated that controlled vaccination for flocks at risk should be included in a multi-prong control strategy alongside enhanced biosecurity, an eradication plan, monitoring, and a repopulation plan.

In a 2016 report, the USDA reported that the stockpiled vaccine wasn’t “well matched” to then-circulating strains. Like influenza in humans, bird flu is a quickly evolving virus. Ensuring that a vaccine is highly effective against H5N1 is the first critical step in a successful vaccination campaign. In 2023, the USDA’s Agricultural Research Service began testing five vaccine candidates. According to the USDA’s website, studies show the candidates provided near 100 percent clinical protection in chickens. (The USDA has also started to “assess the potential to develop” an H5N1 vaccine for cows.) The USDA has not released further information about the clinical trials.

However, despite seemingly having an effective vaccine in hand, as of late April, the USDA is still not pursuing bird flu vaccination as a disease control strategy. “While USDA is exploring the possibility of developing a poultry H5N1 vaccine to stock and use in an emergency, we are not moving forward with a HPAI vaccination program at this time,” a USDA spokesperson told Vox.

Given the scale of the ongoing outbreak, some experts feel that the lack of a vaccine push from the USDA is hamstringing disease control efforts. “I’m a poultry veterinarian, and as a veterinarian, I don’t like the idea that you tell me to go fight the biggest fight of my career and you say, here’s your gun; first, let’s unload it. Now, go,” said Cardona. “A vaccine is simply a tool, and how we use it can be very effective.”

The USDA and industry stakeholders have cited a slew of various challenges that would hinder vaccination.

The biggest sticking point is around trade. The US exported more than $5 billion in poultry meat and products on average every year for the past three years. The USDA enters into trade agreements with each individual country it trades with, explained Upali Galketi Aratchilage, a senior economist at the Food and Agriculture Organization of the United Nations. Each agreement outlines specific biosafety and production requirements that both countries agree to follow. The USDA said, in an email to Vox, that many of those agreements do not allow bird flu vaccination. “For now, biosecurity is the best defense against HPAI,” a USDA spokesperson wrote.

One main reason is the potential to import infected poultry. Vaccination does not prevent infection; it prevents severe disease and death by priming the immune system to better squash pathogens upon infection. By preventing overt flu symptoms such as sneezing, coughing, or reduced egg production, infected birds might then inadvertently enter the food chain. Importing an infected bird could set off new outbreaks, threatening the local supply chain.

But, Cardona explained, the industry no longer relies on diagnosing sick poultry based on visible signs and symptoms but on strict protocols that utilize molecular testing.

Take eggs, for example. Before eggs can enter the food chain, the hens that laid the eggs are tested twice for influenza. Farmers collect samples from the hens the day they lay the eggs and then two days later (the virus spreads so fast that it could be detected in that time). The samples that are collected undergo molecular testing, meaning that scientists look for the genetic fingerprints of the virus in the samples which would be found even in asymptomatic chickens. Not every single hen can be tested, but a random and representative selection is tested each time.

“Markets have been negotiated based on not using vaccination … based on, frankly, older data [that] there could be a chance that you would import the virus in an animal or in a product that has vaccine in it,” Cardona said.

Another concern is differentiating infected from vaccinated animals, the so-called “DIVA” problem. It’s the challenge of identifying whether a bird is actually sick or just has antibodies after vaccination, as Kenny Torrella has previously explained. Again, this seems like an outdated concern as newer technology is capable of differentiating between animals infected with flu versus those that received the vaccine.

Then there’s the logistical challenge that the USDA and other stakeholders cite. The vaccines currently undergoing trials “continue to rely on a two-dose regimen, which can be impractical for distribution to flocks,” the USDA website states. This hurdle does not seem insurmountable, the experts Vox spoke with said, since poultry already receive several vaccines such as those for Newcastle disease, salmonella, and bronchitis. Some vaccines are given through the poultry’s water supply or sprayed in the air. There is even a method where the vaccine is poked through the eggshell and injected into a chicken embryo during development at the hatchery.

Even with biological, technological, and logistical hurdles surpassed, the decision around vaccination seems to be a monetary one. Beyond the cost of vaccination, there’s the potential of losing key trade partners. Trade agreements, especially for meat, are notoriously delicate, in part because of the risk of introducing infectious diseases and pests into a country’s food chain but more so because governments need to protect the agricultural industry from foreign competition. The National Chicken Council is opposed to vaccination efforts. The National Turkey Federation says unilateral vaccination “would have a severe impact on exports” but that it has urged — and continues to urge — the federal government to “move as rapidly as possible to try to develop new agreements” with trading partners.

“Meat is a highly politically sensitive issue for many countries, and the entire livestock industry is protected in many countries for various reasons,” said Aratchilage. Introducing bird flu vaccines is not going to be easy, he added. “It’s a political decision more than a scientific decision.”