Mink in Spain, seals in Scotland, sea lions and dolphins in South America: several species of mammals have recently been found to be infected with H5N1, a highly pathogenic strain of bird flu. Bird flu is not new; Epidemiologists have been studying it for decades. But the detection of the virus in mammals has many concerned that it could spread to humans and cause a larger outbreak.
As the world enters the fourth year of a global pandemic caused by a virus likely to come from an animal, concern about another virus that could upend our lives is valid. H5N1 has infected humans before, although person-to-person transmission has rarely been observed. And while the World Health Organization (WHO) reports While the bird flu mortality rate in humans is around 56 percent, many experts believe it is likely to be much lower if the virus becomes more transmissible. One of the reasons bird flu is so deadly is that it infects the lower respiratory tract, which can lead to respiratory failure. If it were to mutate to infect the upper respiratory tract and spread more easily, it would probably cause milder disease. However, even a virus that causes mild or moderate illness in many people can take a serious toll, as we have seen with the COVID pandemic. Therefore, efforts are underway to develop vaccines that protect against this form of bird flu.
bird flu has spread to humans before—in fact, last week a girl in Cambodia died of H5N1 (although it is not the same strain that is making birds sick all over the world).
“Every time we see this happen, we have these outbreaks of cases, [and] people say, ‘Here it comes; it’s going to happen,’” says Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. But he stressed that H5N1 is likely not an imminent threat to humans.
Others agree. “I follow him closely as an expert, but as a member of the community, as a parent, and as someone who [has been] recently experiencing the COVID-19 pandemic, I’m not concerned about this right now,” says Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security. “This is an animal health problem right now that has a theoretical risk of becoming a human health problem.”
Avian influenza viruses infect birds by binding to a receptor in their respiratory tract. For the virus to become a human virus and start circulating from person to person in the population, it would have to be able to latch on to the human version of this receptor, something it hasn’t evolved to do yet.
“It’s a really dangerous time to be a bird,” adds Andrew Pavia, chief of the division of pediatric infectious diseases at the University of Utah. “But as of today, the risk to humans remains very low. Our concern is what is going to happen as it circulates more and more.”
Unfortunately, it’s almost impossible to predict when this jump might occur. “None of us know when the next influenza pandemic will emerge. It could be tomorrow [or] it could be years from now, and we don’t know which of the viruses will become the next pandemic virus,” says Osterholm. “From the outset it must be said that there is uncertainty, with one exception: there will be a pandemic.”
The United States is somewhat equipped to handle avian flu: there is a stockpile of egg-based flu vaccines for the H5N1 strain. Eggs are one of the most common shapes to make a flu shot. To create it, manufacturers inject an inactivated or weakened virus into a fertilized chicken egg, incubate the egg for a few days while the virus multiplies, and then harvest it for use in the vaccine. The country has a chicken secret reserve at undisclosed locations in the US in case we need to make egg-based vaccines quickly, such as during a flu pandemic. It may be concerning that this vaccination strategy relies on an animal that is highly susceptible to the flu in question. But several experts said american scientist that high levels of biosecurity exist in chicken facilities to avoid contamination by avian influenza.
There are alternatives to egg-based vaccines. Since the early 2010s, the US Department of Health and Human Services has partnered with CSL Seqirus, one of the largest manufacturers of influenza vaccines, to develop vaccines grown in cells in a laboratory. The pandemic preparedness vaccine AUDENZ, which specifically targets the H5N1 subtype, is approved by the Food and Drug Administration. And while it’s impossible to determine which virus will cause the next pandemic, CSL Seqirus has a library of viruses that have the potential to infect humans. And the company is constantly looking for candidate vaccine viruses that it can tailor to a specific pathogen.
“We use data [for] one of the avian strains to create a test file,” says Marc Lacey, who leads CSL Seqirus’ pandemic preparedness and response team. Team members basically identify certain viruses, use them to create vaccines, and do some of the first safety studies so that if a bird flu strain becomes a true human-to-human pandemic strain, they’re ready to use a proper vaccine. Lacey says his company could supply the US government with 150 million doses within the first six months of a pandemic being declared, but he thinks the potential for scale-up could be higher, especially if multiple manufacturers could help produce it. Because there are eight billion people in the world, widespread scale-up and collaboration between countries would be needed to produce enough vaccines.
There are also efforts to apply messenger RNA (mRNA) technology, like the one used for some of the COVID vaccines, to flu vaccines. According to University of Washington microbiologist Deborah Fuller, these efforts range from developing a universal flu vaccine to create a “multivalent” vaccine that targets only a few subtypes—or versions of the virus (as a typical seasonal flu vaccine does). One advantage of mRNA technology is its speed of production. And because of the COVID pandemic, there is now more infrastructure to mass-produce doses. “RNA vaccines can be designed extremely quickly: you just need the genetic sequence of the new variant that is emerging and, in a matter of weeks, [you] you can have a vaccine already tested in animal models”, says Fuller.
Scott Hensley, a professor of microbiology at the University of Pennsylvania, is also investigating mRNA flu vaccines. He is part of a research team developing a 20-subtype mRNA flu vaccine that includes an H5N1 strain (although not the one currently circulating in birds). The team recently published their findings in Science. Hensley’s lab is now developing a single-strain vaccine adapted to the current strain of bird flu and is already testing it in laboratory animals. He stresses that, as with COVID vaccines, his vaccines are meant to prevent serious illness and death, not infections.
But even the 20-subtype vaccine is expected to provide some protection against the new strain. “When we developed [that] vaccine, the idea was to create one that could induce a certain level of immunological memory against each subtype,” says Hensley. “Our goal was not to predict which influenza subtype would cause the next pandemic or which strain would cause it. rather the vaccine [would induce] some level of immunological memory against each subtype to limit disease and death caused by new pandemic strains.
A vaccine is only one part of preparing for a pandemic; you also need effective treatments. As Pavia says, researchers aren’t working from scratch trying to create something like the COVID antiviral Paxlovid, which took nearly two years to come to market. FDA approved antivirals for influenza, such as Tamiflu, already exist and will be important in reducing deaths during an influenza pandemic. Pavia is also hopeful that the US can quickly adapt diagnostic tests to match a pandemic flu outbreak strain.
“We have better tools and better knowledge about influenza than about coronaviruses. In many ways, we would be one step ahead,” says Pavia. “But what worries me is our political response capacity. we need to continue [increase] awareness and continue preparedness efforts. And if things start to pick up speed, we need a concerted, non-politicized effort to act quickly and effectively.”
