The Quest to End the Flu

The methods used to make flu vaccines are slow and sometimes unreliable, and new viruses threaten to outrun them. Can researchers find a way to stay ahead?
Kevin Van Aelst

On April 28, 2009, a box containing a newly isolated virus showed up at Doris Bucher’s lab. She and her colleagues at New York Medical College opened it up right away. Thousands, or perhaps millions, of lives might depend on what they did next.

The virus was a new kind of influenza, known as 2009 H1N1. It had abruptly started spreading across North America in the previous month, and was beginning to appear in countries around the world. Once scientists at the Centers for Disease Control and Prevention analyzed it, they realized that the vaccine already in production for the next flu season probably wouldn’t be effective against it. And because it was so new, people’s immune systems might also be unable to stop the virus, which meant that it could become a global outbreak—a pandemic.

No one knew how bad 2009 H1N1 might prove to be, but the experts did know that the virus had the capacity to be very bad. Flu pandemics had occurred three times in the previous century, and the worst of them, the so-called Spanish Flu of 1918–19, had killed an estimated 50 million people. It, too, was an H1N1 virus. Once researchers at the CDC got hold of the 2009 H1N1 virus, they had one urgent mission: make a new vaccine.

The first step was to send batches of the virus to a handful of vaccine experts like Bucher. As soon as she received her supply of 2009 H1N1, she got to work on creating a “seed stock” of modified viruses that could be used to produce hundreds of millions of vaccine doses. Manufacturers for the most part still make flu vaccines the way they did in World War II: in chicken eggs. Bucher had to transform the viruses, which grow very well in human airways, so that they would grow very well in eggs.

Bucher and her colleagues created a new seed stock using a method more than four decades old, which she has been refining in recent years, as she has helped prepare each year’s seasonal flu vaccine. She and her colleagues drilled tiny holes into the eggs and injected the 2009 H1N1 virus, along with another flu strain that grows well in eggs. The two viruses made copies of themselves in the eggs, and sometimes their genes mixed together, producing hybrids. Bucher’s team harvested the viruses from the eggs and plucked out the best-growing hybrids, reinserting the lines into new eggs. Before long, the team had produced a hybrid that could be used to inoculate people against 2009 H1N1—and could produce 32 times more virus in eggs than the strain Bucher had received in the mail. “We got this thing ready in three weeks,” Bucher told me recently, with the pride of a viral gardener. “It worked beautifully.”

But it was not until October that the first 2009 H1N1 vaccines started trickling into clinics and hospitals. Six to eight months from isolating a new flu virus to putting shots in arms is a typical schedule for a flu vaccine. Unfortunately, the virus didn’t get the memo. Cases of 2009 H1N1 were already skyrocketing in the United States—but the vaccine supply was less than half the projected amount. Many of the people clamoring for the vaccine couldn’t get it.

Bucher’s daughter was one of them. “She had a baby at the end of September, and that meant she was really at risk,” Bucher told me. “My daughter went to a vaccine site on the Upper East Side. The line went for blocks. And then she went home.” Bucher was frustrated to no end that her own daughter couldn’t get the vaccine she had created six months earlier, fewer than 30 miles away.

“I thought, This is really depressing,” says Bucher.

Fortunately, her daughter survived the pandemic, and 2009 H1N1 turned out to be a bullet dodged. In 2012, a CDC-led team of epidemiologists reviewed health records and estimated that only 284,400 people died of H1N1-related complications worldwide in the first 12 months of its wide circulation. “Only 284,400 deaths” may sound like a grotesque downplaying of a huge loss of life, until you consider that the 1918 pandemic killed, according to some estimates, nearly 200 times as many people.

The relatively low death toll was not the result of a hugely effective vaccine that stopped a deadly virus. In a 2013 study, CDC researchers estimated that the vaccine was only 62 percent effective in people younger than 65. (For those older than 65, it was only 43 percent effective.) While that’s far better than zero, it’s mediocre compared with the effectiveness of vaccines for diseases like polio and measles, which can reduce a person’s risk of infection by more than 90 percent.

The ideal is a flu vaccine you use once to be immunized for life. Recent research suggests that the dream of a universal vaccine could come true.

To make matters worse, only an estimated
27 percent of people in the United States ended up getting the vaccine for 2009 H1N1 by April 2010, in part because it didn’t start arriving in sufficient numbers until the end of December. (During last year’s flu season, 45 percent of people older than six months got vaccinated.) So the vaccine was just a modest help for public health: Between
43 million and 89 million people in the United States came down with 2009 H1N1 from April 2009 to April 2010. The vaccine prevented 700,000 to 1.5 million cases. Between 8,870 and 18,310 people in the United States are estimated to have died in the pandemic. The vaccine thus saved 200 to 500 lives.

It turned out that 2009 H1N1 had little trouble spreading, but a lot of trouble killing on a massive scale. A future flu virus might have much less trouble. We have been warned.

The frustrations of 2009 showed experts just how mysterious flu viruses can be, and how much vaccines against them leave to be desired. The sudden outbreak drove home the realization that the world needs vaccines that are more effective and faster to make—not just to reduce the 250,000 to 500,000 deaths from seasonal flu that occur every year but also to prepare for the arrival of new, deadly pandemics. Many researchers became convinced that it was time to step beyond World War II–era technology and start using 21st‑century methods for making vaccines. “The eggs should be long gone,” grumbles Michael Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

In the four years since the 2009 pandemic, researchers have been searching furiously for a better answer. This year saw the publication of a string of papers that could lead scientists to a fundamentally new kind of flu vaccine—one that might someday substantially reduce the impact of a pandemic, and save many lives that would otherwise be lost to seasonal flu.

Most scientists call it a universal flu vaccine, because it would protect people against many flu strains, including ones that have yet to evolve. This universal vaccine could ultimately put an end to the annual ritual of getting a flu shot: each jab might protect for years or even a lifetime.

It could take years, even a lifetime, before a universal flu vaccine becomes available. Still, the mere fact that it could become a reality marks an important shift in the fight against influenza. “We don’t have them ready to go tomorrow,” says Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, of the next generation of vaccines. “But we didn’t even have them at the concept stage in 2009.”

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Carl Zimmer writes about science regularly for The New York Times and magazines such as Discover, where he is a contributing editor and columnist.

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