If bird flu spreads to humans, existing vaccines may be inadequate

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

It is the largest outbreak of this type of bird flu, known as H5N1, since it was first identified in China in 1996.

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

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

Vaccines for people, meanwhile, would only be considered if the virus eventually undergoes a complicated series of mutations that allow it to spread from person to person. There is no proof of this yet. The United States recorded its only human case of H5N1 last April – the person was involved in the slaughter of suspected infected poultry in Colorado. The UK reported two cases on Tuesday, both of 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 vaccines in case such a crisis arises, but three experts have said it is likely to be insufficient if this particular type of bird flu starts infecting people. The injections were only given in trials and were from strains that circulated in 2004 and 2005.

“You would expect these vaccines based on these older strains to probably offer little protection against what’s circulating today,” said Scott Hensley, professor of microbiology at the University of Pennsylvania.

Developing new vaccines better suited to the current strain would be complicated, however, as most flu vaccines are grown in chicken eggs – “a slow process fraught with production issues”, according to Dr Gregory Poland, founder and director. from the Mayo Clinic’s Vaccine Research Group. The process requires each egg to be individually inoculated with a modified virus and, of course, depends on a sufficient supply of healthy chickens.

“In a real pandemic situation, poultry will be at risk and then the egg supply will be severely compromised,” said Dr Suresh Mittal, professor of virology at Purdue University. The United States, however, maintains a stock of chickens to ensure it can continue to produce flu shots.

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

“What we need is a library of ready-to-use H5N1 vaccine candidates,” Poland said, adding that “we are putting people and economies at cataclysmic risk by not being prepared. “.

Preparing for a spillover on humans

In general, scientists begin to worry about the spread of bird flu to humans when there is mammal-to-mammal transmission, Hensley said. Scientists saw proof of this in an October outbreak in mink in Spain.

“We are concerned that these kinds of events could lead to a mutant form of this virus that could be transmitted between humans,” Hensley said.

Since arriving in the United States last January, avian flu has spread from birds to several other mammals: cougars, bobcats, bears, seals, red foxes, coyotes, raccoons, skunks and opossums, as well as a otter and a bottlenose dolphin.

Poland likened these infections to the “rumblings before an earthquake”.

He suggested that a bird flu pandemic would most likely start with a small outbreak among poultry or pig workers, as pigs can transmit the virus from birds to humans. Such an outbreak could be contained immediately, he said — or not.

Vaccine researchers are therefore preparing. Moderna said later this year it plans to begin clinical testing of an mRNA vaccine specific to the strain currently circulating in birds, called 2.3.4.4b. mRNA technology offers an advantage because it allows rapid production and updating of vaccines. Since experts believe that a future bird flu pandemic would be caused by a strain of H5N1 that has yet to evolve, ideal vaccines could be easily modified to target it.

Hensley leads a research team testing another mRNA vaccine to target 2.3.4.4b. Data published in April, which has not been peer-reviewed, showed it elicited an immune response in mice and ferrets.

“Making a vaccine that resembles what’s currently circulating gives us a better chance of having cross-protection against something slightly different, but very related,” Poland said.

Meanwhile, two other pharmaceutical companies, CSL Seqirus and GSK, have teamed up with the US government to manufacture experimental vaccine doses that also more closely match the current strain. GSK’s trial is expected to begin this year, but the company did not specify what kind of technology it uses. CSL Seqirus said a Phase 2 trial to assess the safety and immune response of an inactivated virus vaccine is expected to begin in June.

Mittal said a universal flu vaccine that targets a wide variety of flu strains could also provide cross-protection against any version of bird flu that one day finds its way into humans. Several of these vaccines are in development, but none have reached an advanced stage of testing. The National Institutes of Health announced this month that they had begun testing a universal mRNA flu vaccine among 50 volunteers.

Could old vaccines be updated?

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

One such vaccine, from pharmaceutical company Sanofi, was approved for adults in 2007. In a trial of about 100 people, two doses elicited a protective immune response in 45% of recipients, according to the Food and Drug Administration. . In 2007, the United States had enough of this vaccine stocked for 6 million people.

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

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

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

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

A GSK spokesperson said the company secured contracts last year with the United States, Canada, the European Union and the World Health Organization to supply its pandemic flu vaccine. . Under these agreements, the spokesperson said, the company could provide at least 200 million doses to governments around the world.

The third stock vaccine, from CSL Seqirus, was approved in 2020 for recipients aged 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 these antigens that cross-react with circulating strains could be formulated into doses, he said.

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

But Poland said even those promises from manufacturers would still fall short of the Biden administration’s national biodefense strategy, which aims to produce enough vaccines for the entire United States within about four months of the start. of a future pandemic.