H5N1 and spillover risk: Is the world ready to tackle zoonotic influenza?

One of the most timely, engaging and well-received panel discussions at the CEPI co-hosted Global Pandemic Preparedness Summit 2024 in Rio de Janeiro in July was one led by the international pandemic preparedness and response expert Dr Rick Bright. Dr Bright is also a former director of the U.S. Biomedical Advanced Research and Development Authority (BARDA).

In the session, Dr Bright invited experts in vaccinology, epidemiology, surveillance and outbreak response to explore the question: Zoonotic influenza—would we be ready for an equitable 100- day response and what can we do to prepare?

Afterwards, CEPI’s Kate Kelland caught up with Dr Bright to ask for his insights on the current outbreak of H5N1 bird flu, otherwise known as H5N1 avian influenza, among cattle and poultry in the United States and on whether the global health security system is moving swiftly and effectively to counter its threat.

(The interview has been lightly edited for clarity)

Q: Can you start by describing the sort of situation we’re now in with H5N1, and how much of a risk it is?

A: With H5N1, the risk is increasing daily. It’s a virus that we’ve known about for a long time, and historically it has infected about 950 people who have had direct contact with a sick animal, a sick bird for example. And in that population (of direct contacts) about 52 percent of the people have died. Now we find ourselves in a very different situation, because this virus has not only infected wild birds, it has also infected domestic poultry – turkeys and chickens – and now it has spilled over to dairy cattle in the United States.

The problem with that situation is that there are a lot of people who work daily in constant interaction with these dairy cattle, so the exposure level of people working with these infected animals is increased. The chance for infection and spillover in the people is increased. And the chance for the virus to mutate is increased. 

In the general population, the risk is somewhat low because we're not all milking cows, but in those people who work very close to these infected animals, the risk is very high. And the spillover risk is this: the more people infected, the more chance for mutation, and the more chance that this will change rapidly and get out of control and could be a deadly virus. 

Q: Is this situation one that is already a crisis, or is it something where we should be sounding the alarm and responding to that alarm?

A: The alarm is sounding. This is an unprecedented outbreak that we see now in domestic mammals. It's in dairy cattle, it’s in cats, it's in mice, and now it's spilling over from those animals, those domestic mammals, back into birds. It's affecting marine wildlife as well—and more people.

So the alarm bells are going off. There are things we should be doing and we're not, and we're not even being as transparent as we should be with the data that we might be collecting to inform how alarming this might be. 

Some people want to hit the snooze, and others want to take concrete actions to be ready, to make sure that we can respond in an equitable way when this takes off. 

Q: And at this point, would you say that we are ready? Are we better prepared than we have been in the past for a zoonotic flu outbreak? Could we respond with an effective 100 Days Mission response?

A: No, we're not ready. We could not respond with an equitable response. If we had an outbreak of avian influenza today, we would not have enough vaccines ready and available to distribute globally, especially to low- and middle-income countries, who were also last in line in the last influenza pandemic (of H1N1 influenza in 2009). They waited almost a year to get their vaccine. Nothing has changed since then. We wouldn't have enough diagnostics to be able to conduct the surveillance to inform countries of the risk. We wouldn't have enough therapeutics and drugs available, we wouldn't have enough masks and PPE and respiratory protection. There's a lot of work that needs to be done.

At the same time, I would say we are more prepared - because we spent a lot of money (on this) 25 years ago. We spent billions of dollars. We built manufacturing capacity around the world. We've done a lot of things, but a lot of it is outdated. A lot of it could be improved on with modern technologies and modern tools. But we do have to invest.
  
And we have to invest in it with an eye on equity. Not an eye on a charitable donation from high income countries that would donate what's left when it's already expired, but an eye on equity first. That's the only way we're going to ever be ready for an equitable response to a pandemic. 

Q: What three things would you like to see happening right now to get us closer towards that state of readiness to be able to respond?

A: Well, we just had an excellent panel of experts (at the July 29th-30th 2024 Global Pandemic Preparedness Summit in Brazil) and I asked them what one thing they would like to see to get us there, to make us more ready for an equitable response. One of the most predominant statements was surveillance. We have to not just think about surveillance in the human population. We have to think about surveillance in the animal population, those animals at high risk for spillover and spill back from humans to animals as well in wildlife. We're not doing enough surveillance there, and that's critical. We have to know what's coming at us, where it is, how it's changing -- or we can't do anything about it until it's too late.

Another thing would be to make sure that we are modernizing our vaccine approaches. You know, we can't rely on a 1940s technology—an egg-based influenza vaccine—for a 2024 emergency response. There are new tools. We have new vaccines. We have super powerful computing capabilities to understand how we can make the vaccines better. So we need to make better vaccines.
 
The third thing I would say is we have to think about how those vaccines are administered. It can't be a needle and syringe in a super-cold freezer storage where very few places have that capability. We have to think about access as well as production. Can we change the vaccines for mucosal delivery, oral delivery, intranasal delivery or transdermal delivery? Can we make the vaccines more room stable, so they don't require cold storage? Can we make the vaccines cross-protective? So that as the virus changes, we're not chasing the virus anymore, but we're out there in front of it with a vaccine that's going to keep it from changing. 

Those are three critical things we can do right now with innovation, technology and equity in mind first that would make a huge difference for an equitable response to a pandemic.