Wild birds and poultry flocks continue to die from highly pathogenic avian influenza that began to spread globally in 2020. Nearly 59 million commercial birds have already been culled in the United States.

Is he wider outbreak of this type of bird flu, known as H5N1since it was first identified in China in 1996.

The proliferation of the virus and the high mortality rate have raised questions about two types of possible vaccines: those for birds and those for humans. H5N1 kills almost all the birds it infects; Among the cases reported in people since 2003, the the mortality rate has been 56%.

The US Department of Agriculture Announced in April that it had begun testing several candidate poultry vaccines.

Vaccines for people, meanwhile, would only be considered if the virus ultimately undergoes a complicated series of mutations that allows it to spread from person to person. There is no evidence of that yet. United States registered its only human case of H5N1 last April: the person participated in the culling of poultry with suspected infections in Colorado. The United Kingdom reported two cases on Tuesday, both poultry workers with asymptomatic infections detected through routine testing. Chile reported one infection in March and Ecuador one case in January.

But scientists have long considered H5N1 to have pandemic potential. The United States has a stockpile of H5N1 flu vaccine in case such a crisis arises, but three experts said it would likely be insufficient if this particular type of bird flu began to infect people. The injections were only given in trials and were derived from strains that circulated in 2004 and 2005.

«One would expect that those vaccines based on those older strains would probably offer little protection against what is circulating today,» said Scott Hensley, a professor of microbiology at the University of Pennsylvania.

However, it would be difficult to develop new, better-adapted vaccines for the current strain, because most flu vaccines are grown in chicken eggs, «a slow process fraught with production problems,» according to Dr. Gregory Poland, founder and director of the Mayo Clinic Vaccine Research Group. The process requires individually inoculating each egg with a modified virus and, of course, relies on an ample supply of healthy chicks.

«In a real pandemic situation, poultry will be in jeopardy, and then the egg supply will be very compromised,» said Dr. Suresh Mittal, a professor of virology at Purdue University. However, the US maintains a reserve of chickens to ensure that it can continue to produce flu vaccines.

Better options may be on the horizon. Vaccine researchers are developing shots that could be updated to target any mutated strain of H5N1 that one day takes hold in people. But there are no human trials underway yet.

«What we need is a library of ready-to-use H5N1 vaccine candidates,» Poland said, adding: «We are putting people and economies at risk of cataclysm by not being prepared.»

Preparing for a contagion to humans

In general, scientists start to worry that bird flu will spread to people when there is mammal-to-mammal transmission, Hensley said. Scientists saw evidence of that for a October outbreak in minks in Spain.

“We fear that those types of events will lead to a mutated form of this virus that could be transmitted between humans,” Hensley said.

Since it arrived in the US last January, bird flu has spread from birds to various other mammals: cougars, bobcats, bears, seals, red foxes, coyotes, raccoons, skunks and opossums, plus an otter and a bottlenose dolphin.

Poland compared these infections to «the rumble before an earthquake.»

He suggested that an avian flu pandemic would likely start as a small outbreak among poultry or swine workers, since pigs can transmit the virus from birds to humans. Such an outbreak could be contained immediately, she said, or not.

So vaccine researchers are preparing. Moderna said that later this year it hopes to begin clinical trials of an mRNA vaccine specific to the strain now circulating in birds, called mRNA technology offers an advantage because it allows vaccines to be rapidly produced and updated. Since experts believe that a future bird flu pandemic would be caused by a strain of H5N1 that has not yet evolved, ideal vaccines could easily be modified to target it.

Hensley leads a research team that is testing another mRNA vaccine to target Data posted in aprilwhich has not been peer reviewed, showed that it elicited an immune response in mice and ferrets.

«Making a vaccine that looks like the one that’s circulating right now gives us a higher chance of having cross-protection against something slightly different, but very related,» Polonia said.

Meanwhile, two other pharmaceutical companies, CSL Seqirus and GSK, have partnered with the US government to manufacture experimental doses of vaccines which are also closest matches to the current strain. GSK’s trial is scheduled to begin this year, but the company did not specify the type of technology it uses. CSL Seqirus said that a phase 2 trial to assess the safety and immune response of an inactivated virus vaccine is scheduled to start in June.

Mittal said a universal flu vaccine, which would target a wide variety of flu strains, could also provide cross-protection against any version of bird flu that might one day reach humans. Several such vaccines are in development, but none have advanced to a late-stage trial. The National Institutes of Health announced this month which has begun testing a universal mRNA flu vaccine among 50 volunteers.

Could older vaccines be updated?

The Department of Health and Human Services declined to specify the number or manufacturers of bird flu vaccine products in the national stockpile. However, NBC News verified that three approved H5N1 vaccines have been stored, two of which are produced from eggs.

One such injection, from the pharmaceutical company Sanofi, was approved for adults in 2007. In a trial of about 100 people, two doses caused a protective immune response in 45% of recipients, according to the Food and Drug Administration. As of 2007, the US had stored enough of that vaccine for 6 million people.

When tested against strains circulating in 2016 and 2017, the vaccine elicited a modest antibody response, according to a study 2019.

However, one dose is 90 micrograms, much larger than the seasonal flu vaccine. In a pandemic situation, that could make it difficult to quickly make shots for everyone who needs them, Polonia said.

«You have to produce the equivalent of six normal doses for one dose of that H5N1 vaccine,» he said. «Those become real numbers when you’re talking about tens and hundreds of millions of people.»

The FDA approved a second injection for adults in 2013, made by a GSK subsidiary, to add to the reserve. The company saying in 2006 that two doses produced a strong immune response in 80% of recipients.

A GSK spokesman said the company won contracts last year with the US, Canada, the European Union and the World Health Organization to supply its vaccine in the event of a flu pandemic. Under those deals, the spokesperson said, the company could provide at least 200 million doses to governments around the world.

The third stored injection, from CSL Seqirus, was approved in 2020 for recipients 6 months and older. It is grown in cultured cells instead of eggs.

The company said the United States has stockpiled millions of doses of bulk antigen, the vaccine ingredient that stimulates an immune response, targeting a variety of strains. In the event of an avian flu pandemic, any of those antigens that cross-react with circulating strains could be formulated in doses, he said.

The company added that it could produce 150 million doses in six months.

But Poland said even these manufacturer promises would still fall short of the Biden administration’s commitment. National Biodefense Strategywhose goal is to produce enough vaccine for the entire US in about four months from the start of a future pandemic.