Mink in Spain, seals in Scotland, sea lions and dolphins in South America: some mammal species 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. However, the detection of the virus in mammals has many worried 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 that likely originated in an animal, the worry about another virus that could uproot our lives is valid. H5N1 has infected humans in the past, although human-to-human transmission has rarely been observed. And while the World Health Organization (WHO) says the fatality rate of bird flu in humans is around 56%, many experts believe it is likely to be much lower if the virus becomes more contagious. One reason 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 likely cause milder disease. However, even a virus that causes mild or moderate illness in many people can have a severe impact, as we have seen with the COVID pandemic. Thus, efforts are being made to develop vaccines to protect against such a form of bird flu.
Bird flu has spread to humans before — in fact, just last week a girl in Cambodia died from H5N1 (though it’s not the same strain that sickens birds worldwide).
“Every time we see this happen, we have these outbreaks of cases, (and) people say, ‘Here it comes. it will happen,” says Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy. However, he stressed that H5N1 likely does not pose an immediate threat to humans.
Others agree. “I’m watching it closely as a specialist, but as a member of the community, as a parent and someone who (has) recently experienced the COVID-19 pandemic, I’m not worried about it right now,” says Caitlin Rivers, an epidemiologist at the Johns Hopkins Center for Health Security. “This is an animal health issue right now that has a theoretical risk of becoming a human health issue.”
Avian influenza viruses infect birds by attaching to a receptor in their respiratory tract. In order for the virus to become a human virus and start circulating from person to person in the population, it must be able to attach to the human version of this receptor – something it has not yet evolved to do.
“It’s a really dangerous time to be a bird,” adds Andrew Pavia, chief of pediatric infectious diseases at the University of Utah. “But as of today, the risk to humans remains very low. Our concern is what’s going to happen as it circulates more and more.”
It is unfortunately almost impossible to predict when this jump might occur. “None of us knows when the next flu pandemic will occur. 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. “In the beginning, you have to say there is uncertainty, with one exception: there will be a pandemic.”
The US is somewhat equipped to handle bird flu: there is a stockpile of egg-based flu vaccines for the H5N1 strain. Eggs are one of the most common ways to make a flu vaccine. 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 replicates, and then harvest the virus to use for the vaccine. The country has a secret stockpile of chicken in undisclosed locations across the US in case we need to make egg-based vaccines quickly – like during a flu pandemic. It may be worrying that this vaccine strategy depends on an animal being highly susceptible to the flu in question. But many experts said Scientific American that there are high levels of biosecurity in chicken facilities to prevent avian influenza contamination.
There are alternatives to egg-based vaccines. Since the early 2010s, the US Department of Health and Human Services has been working with CSL Seqirus, one of the largest manufacturers of influenza vaccines, to develop vaccines grown in cells in a laboratory. The AUDENZ pandemic preparedness vaccine, which specifically targets the H5N1 subtype, has been approved by the Food and Drug Administration. And while it is 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’re using data (on) one of the bird strains to create a mock file,” says Marc Lacey, who heads CSL Seqirus’ pandemic preparedness and response team. Team members basically identify certain viruses, use them to create vaccines, and conduct some of the early safety studies so that if a strain of bird flu develops into a true pandemic strain that spreads between humans, they’ll be ready to move forward with an appropriate vaccine. Lacey says his company will be able to supply the US government with 150 million doses within the first six months of a pandemic being declared, but he believes the potential for scaling up could be greater, especially if multiple manufacturers could help in its production. Because there are eight billion people in the world, scaling up and widespread cooperation between countries would be necessary to produce enough vaccine.
Efforts are also underway to apply messenger RNA (mRNA) technology—such as that used for some of the COVID vaccines—in flu vaccines. According to University of Washington microbiologist Deborah Fuller, these efforts range from developing a universal flu vaccine to creating a “multipotent” vaccine that targets only a few subtypes or variants of the virus (as a standard seasonal flu vaccine does). An 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 emerging new variant, and within weeks, (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 researching mRNA flu vaccines. He is part of a research team developing a 20-mRNA subtype flu vaccine that includes an H5N1 strain (though 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 from the current bird flu strain — and is already testing it in lab animals. He stresses that, as with the COVID vaccines, his vaccines are intended to prevent serious illness and death, not infection.
But even the 20-subtype vaccine is expected to provide some protection against the new strain. “When we developed (this) vaccine, the idea was to create one that could induce a certain level of immune memory against each subtype,” says Hensley. “Our goal was not to predict which subtype of influenza would cause the next pandemic or which strain would cause it. Rather the vaccine (would induce) some level of immune memory against each subtype to limit illness and death caused by new pandemic strains.”
A vaccine is only part of pandemic preparedness—you also need effective treatments. As Pavia says, researchers aren’t working from scratch trying to create something like the Paxlovid antiviral for COVID, which took nearly two years to get to market. FDA-approved antivirals for influenza, such as Tamiflu, already exist and will be important in reducing deaths during an influenza pandemic. Pavia also hopes the U.S. could quickly adapt diagnostic tests to match an outbreak strain of pandemic flu.
“We have better tools and better knowledge about influenza than we do about coronaviruses. In many ways, we would be a step ahead,” says Pavia. “But what worries me is our political capacity to respond. We must continue to (increase) awareness and continue preparation efforts. And if things start to accelerate, we need a concerted, non-politicized effort to move quickly and effectively.”
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