Federal scientists are gearing up to test the first vaccines in poultry against bird flu in years, as Biden administration officials say they have now begun weighing an unprecedented shift in the U.S. strategy to counter the growing outbreak.

The move comes amid mounting concern over the threat posed by the ongoing spread of highly pathogenic avian influenza over the past few years, which has devastated flocks of wild and commercial birds around the continent. 

A record 58 million birds — mostly commercially-raised poultry — have died in the outbreak so far, according to figures tallied by the USDA’s Animal and Plant Health Inspection Service — either killed by the virus itself or put down in efforts to quash its transmission. Every state has detected the virus spreading among wild birds and 47 have spotted them in poultry. 

“The decision to proceed with vaccination is complex, and many factors must be considered before implementing a vaccination strategy,”  USDA spokesperson Mike Stepien said in a statement, adding that the inspection service is discussing the options and “soliciting input from many different industry stakeholders that would be impacted.” 

While the Biden administration has so far not greenlighted the use of vaccines for highly pathogenic avian influenza, several shots had been licensed for potential use in previous outbreaks. Poultry are already regularly vaccinated for other diseases, like infectious bronchitis.

While animal vaccines can take years to be licensed, Stepien said some parts of the process can be accelerated for emergencies. 

It is not yet clear whether vaccines are available that will work against clade 2.3.4.4b, the strain behind the current outbreak in the U.S.

“There are a lot of moving parts to this kind of testing. And some of it is just pure logistics of getting everything in place to do the testing, getting the vaccines that are updated, getting things from parties that are involved, different manufacturers,” said Erin Spackman, a virologist who studies avian influenza vaccines at the USDA.

While it is not always a requirement for animal shots to be licensed by the department, the trials will offer an early independent evaluation of how well a vaccine works in this case. Antibody studies suggest earlier vaccines might not be as well-matched against the strain now driving the current outbreak, prompting the need for tests.

“On the test, it’s a twofold reduction, but that makes it sound a lot closer related than it is. In vaccine-speak, it means it’s starting to drift away,” said Spackman.

Spackman said evaluating the vaccines can take three months, from when birds get their shot — often in the back of the neck or thigh — to studying their response to the virus after immunity develops.

Vaccine makers say they are also closely tracking deliberations by the U.S. and other countries over the possibility of poultry vaccination, as well as assessing their own shots.

A spokesperson for Merck Animal Health said the company has an “extensive, ongoing research program” developing vaccines that can work with so-called Differentiating Infected from Vaccinated or DIVA strategies — an approach that involves systematically hunting for the virus among vaccinated flocks, in hopes of preventing undetected spread among immunized birds.

When to vaccinate poultry?

Officials have so far been wary of deploying vaccines against the outbreak, citing concerns that the use of the shots could make it harder to export American poultry products. 

“What is the trigger point of when you might use vaccination? And that’s what they’re looking at. Is it so many birds in a poultry farms in an area getting infected? Or is it a certain amount of economic loss? Or is it because a neighboring state has the virus in poultry, and you’re concerned? So there’s those are really the tough, tough questions,” said poultry veterinarian David Swayne.

Before retiring to become a consultant, Swayne served for nearly three decades in the USDA’s infectious disease arm and was the director of the department’s top research facility for dangerous pathogens.

Swayne noted there are several high-income countries in Europe that are “further along” in exploring DIVA strategies that would work with poultry exports, after wrestling for years with their outbreak. Others, including Indonesia and China, have already rolled out poultry vaccinations for bird flu.

Under one approach, birds who die of any cause in a vaccinated flock could be aggressively tested for the virus, Swayne said, or live birds might be systematically sampled for antibodies in their blood through a more complex process. Surveillance may also be possible through swabbing the environment, like checking the containers birds drink water from.

“We want to make sure our partners understand that, if we use them, we’re going to use them in the right the right manner so that they can feel secure and safe that the products they buy are not products that might contain, say, a highly pathogenic avian influenza virus,” said Swayne.

Authorities would also need a way to coordinate tracking viruses for updates to the vaccines, potentially similar to how the World Health Organization issues recommendations for manufacturers of human flu shots to keep pace with the latest strains.

However, Swayne cautioned that poultry producers will still need to take steps to shield their flocks from contact with wild birds and other ways the virus could spread.

Like their counterparts abroad, American wildlife officials have spotted the virus decimating groups of birds across a range of species. Officials believe the virus is largely being transmitted to commercial poultry flocks by wild birds migrating across the Americas.

“Biosecurity really is the first line of defense, and any vaccination that might be done is only sort of another layer of protection, sort of an insurance policy,” he said.

Is it a threat to humans?

Authorities say the risk the virus poses to humans seems to be low for now, despite a 56% fatality rate among the handful of people who have tested positive after direct contact with infected birds. 

Out of more than 6,000 poultry workers that American health authorities have tracked after exposure to infected birds, only one has tested positive for the virus. 

Regardless, officials have urged Americans to avoid handling dead or sick birds to reduce their risk. The virus has spilled over from birds to other species, often from coming into contact with the carcasses of infected birds.

“Somewhat concerning is that there’s been transmission to mammals in a variety of terrestrial mammals, which are basically the most of them are predatory mammals,” the Centers for Disease Control and Prevention’s Tim Uyeki told a webinar hosted by Emory University last month.

The federal Administration for Strategic Preparedness and Response also already maintains a program with vaccinemakers to “make and test small quantities” of shots for humans that can be ramped up to large-scale production if needed.

“High on my radar. We’ve already been in touch with our teams as to where we are with both surveillance and detection, as well as our USDA colleagues on the detection in the avian population as well,” CDC Director Dr. Rochelle Walensky told a panel of the agency’s advisers this week.