The infection of dozens of cattle herds in the U.S. with the avian influenza virus H5N1 has raised concerns about whether the pathogen, which frequently infects poultry and wild birds, could spread more widely in humans. While the virus has circulated in birds many times in the past few years, it is now infecting mammals that come into contact with humans on a regular basis.
“The concerning part is: there seems to be a lot of human contact with these viruses through cattle,” says Scott Hensley, a professor of microbiology at the University of Pennsylvania. “That could change the equation very quickly.”
The Centers for Disease Control and Prevention and many experts maintain that the public health risk is still very low. And in the U.S. only two cases have ever been reported in humans, one of whom was infected with the strain that is currently circulating in cattle. Nevertheless, the federal government, pharmaceutical companies and researchers are all preparing in case mass vaccination of people against H5N1 ever becomes necessary.
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“We’re ahead of the game in terms of avian flu vaccine, compared to where we were with COVID,” says Shira Doron, chief infection control officer at Tufts Medicine and a hospital epidemiologist at Tufts Medical Center. But experts have expressed concerns about the U.S.’s ability to create and distribute enough vaccines, as well as about the question of whether the vaccines will hold up against circulating strains.
The CDC is constantly screening circulating bird flu strains and updating vaccines accordingly. There are currently two candidate vaccine viruses that are well matched to the currently circulating strain. The National Pre-Pandemic Influenza Vaccine Stockpile has around several hundred thousand filled vials and syringes that could be deployed during an initial wave of vaccination. And these vaccines are not that old: they are left over from recent and ongoing clinical trials, says David Boucher, director of infectious disease preparedness and response at the Administration for Strategic Preparedness and Response (ASPR).
ASPR also has materials on hand to make additional vaccines. “We have a pretty large stockpile of bulk antigen [the part of the virus that a vaccine targets], and we also stockpile adjuvant [a substance that increases the body’s immune response to the vaccine] so that we have the two main building blocks of vaccines if we need to pivot over to manufacturing,” Boucher says. He estimates it would be the equivalent of several million doses, produced over three to four months.
The U.S. government also has partnerships with three pharmaceutical companies: GSK, CSL Seqirus and Sanofi. These companies have seasonal influenza production capacity and say they would be able to scale up production of avian flu vaccines if needed.
“We would have to weigh this against interrupting seasonal [flu vaccine] production, but if we did enter into that, we would be looking at tens of millions of doses available in the next four or five months—approximately over 100 million in the first four months of production,” Boucher says.
But there are some nuances that would make it difficult to scale up an avian flu vaccine, Doron says. For one, the current candidate vaccines are egg-based, which is a bit of a logistical issue: the virus can kill the chickens that produce the eggs needed for a flu vaccine. The U.S. keeps a secret chicken stockpile to avoid any contamination and maintain security, however. “We have a supply of eggs that has a biosecurity fence around it, so we’re not, at this moment, concerned about supply of eggs,” Boucher says.
Candidate bird flu vaccines can be used in both egg- and cell-based cultures (which are grown in a lab dish), says Luis Martinez-Sobrido, a molecular biologist at the Texas Biomedical Research Institute, who is currently working on such vaccines in conjunction with the CDC.
CSL Seqirus manufactures an FDA-approved cell-based H5N1 vaccine called AUDENZ. According to a company spokesperson, CSL Seqirus’s vaccine manufacturer, located in North Carolina, could deliver up to 150 million doses of cell-based pandemic influenza vaccine within six months of an influenza pandemic declaration.
There is also some skepticism about how vaccines would hold up against newer strains of H5N1. Just as the virus that causes COVID mutates and necessitates updates to the vaccine, so, too, would H5N1.
“It’s one of the concerns that we have anytime we have a virus percolating in a new species,” Boucher says. “But where we are right now, with the candidate vaccine virus that’s well matched, we would not expect a rapid decline in effectiveness if we used it.”
Additionally, a recent report from the New England Journal of Medicine revealed that the H5N1 virus in the dairy farmer who was recently infected had a gene that affects how the pathogen binds to cells that is commonly associated with viral adaptation in mammals, and also had proteins very closely related to that of the evolutionary group of the virus that is targeted by the existing candidate vaccine.” This bodes well for the ability of the vaccine to protect humans, at least against severe illness and death.
One way to counter mutating viruses is by creating a messenger RNA, or mRNA, vaccine like those developed to protect against COVID because it could be easily tailored toward circulating strains. “When you’re tracking a virus that can evolve, you would like to be able to pivot quickly,” Boucher says, noting that adaptability was key for the COVID vaccines. “When that virus evolved to a place where it was a little too different from the vaccine we were using, we changed the sequence of the mRNA.”
Boucher says that his team at ASPR has sent a solicitation out to companies who might be able to partner with the group and that he and his colleagues may have more to announce in the coming weeks.
Biotech company Moderna is conducting a phase 2 trial of an mRNA vaccine that targets the same evolutionary group as the avian influenza virus that is causing outbreaks in the U.S. The company believes it could be adapted easily to new mutations.
“As we’ve seen with our COVID-19 vaccines, one feature of our mRNA platform is that vaccines can be quickly updated to address the latest strains,” wrote a spokesperson for Moderna in an e-mail to Scientific American.
Academic researchers are also working on developing their own mRNA vaccines. Hensley and his colleagues have posted a preprint paper, which was recently accepted for publication in a scientific journal, that demonstrated that their mRNA H5N1 vaccine elicited very strong immune responses in both mice and ferrets. It hasn’t been tested in humans, though.
“The vaccine appears to do what it is designed to do, [which] is to elicit very strong neutralizing antibodies against these new H5 clades [evolutionary groups] and to protect animals from infection,” Hensley says. (He notes that the virus has mutated a bit since the studies began but that the changes are fairly minor, and the vaccine can be updated accordingly.)
Experts emphasize vaccines are also just one part of a pandemic response. Behavioral changes are also key to reducing viral transmission.
“This is definitely not a panic-worthy situation,” Doron says. “But there are things that all people should be doing, and then there are some things that people who work with animals should be doing.” She advises the general public to avoid unpasteurized milk and to limit contact with wild or farm animals. She adds that those who come into contact with these animals should wear personal protective equipment.
Both Doron and Martinez-Sobrido emphasize the importance of validating and developing new antiviral medications for H5N1. The virus is likely susceptible to current flu treatments such as Tamiflu, but researchers have highlighted the need for more robust antivirals.
“If this virus jumps to humans, it’s going to take a while for the CDC to produce [a] large amount of the vaccines to vaccinate everybody,” Martinez-Sobrido says. “We need drugs that will be our first line of defense against the virus until everybody has access to the vaccine.”