A century after one of the world’s deadliest pandemics, annual flu shots could soon be a thing of the past
In1918, in the final months of World War I, a flu pandemic spread across the world. It may have started among Chinese laborers who were transported in trains across Canada, and was first identified in the U.S. in soldiers. In the absence of vaccines, or antibiotics to treat secondary bacterial infections, the pandemic would eventually infect 500 million people and kill 50 million — 3% of the global population — making it the deadliest pandemic in history after the Black Death.
Twenty years later, legendary immunologist Jonas Salk and his New York University mentor Thomas Francis developed the first flu vaccine. Their discovery, which was first tested on U.S. soldiers in World War II, laid the groundwork for Salk’s revolutionary later work on a polio vaccine.
But in the mid 1940s, as the vaccine became publicly available, researchers began to notice a troubling trend: For reasons that are still not entirely understood, the genes of the flu virus tend to “drift” year to year, creating slight mutations that can render last year’s vaccine ineffective. That’s why the flu season is a never-ending game of immunological whack-a-mole, in which scientists at the World Health Organization (WHO) and other agencies — like the U.S. Centers for Disease Control (CDC) — make an informed guess about what change might occur and preemptively design a new vaccine to protect against the new viral strains.
For the most part, they’ve been remarkably successful: The seasonal death rate from flu in the U.S. in the 1940s was around 10 per 100,000 people; by 2017, it was around two. But the disease still sickens up to five million people globally each year. In most seasons, the vaccine works less than half of the time.
Now, a century after the pandemic, scientists are closing in on the ultimate prize in immunology: a so-called universal flu vaccine that would counter most, if not all, flu strains and would need to be administered only once in a lifetime.
Researchers at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland, are in the middle of a human trial of a promising new universal flu vaccine, the latest in a recent spate of trials to commence after federal health officials released a new universal flu vaccine development strategy last winter. The trial involves more than 50 healthy adults, ages 18 to 70, who will be given the vaccine and then have a sample of their blood exposed to the virus to gauge its immune response. So far 30 people have received the vaccine.
There’s no one single scientific breakthrough behind the recent progress. Instead, the NIH trial represents the culmination of several decades’ worth of incremental research on the molecular structure of the flu virus, how it changes over time, and how to manipulate it in the interest of triggering a protective immune response.
“This new NIH trial is a great example of how much vaccine platforms have advanced over the years,” says Andrew Pekosz, an immunologist at the Johns Hopkins Bloomberg School of Public Health, who is not involved in the trial.
“The experience my family has had with the flu is a great motivator to me, personally… I really hope they’re on to something.”
The vaccine works by targeting a different part of the virus than flu vaccines traditionally have. Influenza viruses carry a specialized protein known as hemagglutinin, which allows the virus to attach to and enter human cells, and which is folded into a lollipop-like shape, with a round “head” attached to a slender “stalk.” Historically, flu vaccines have worked by prompting a person’s body to develop antibodies that target the head, mirroring humans’ natural immune response to flu infection.
But over the last two decades, scientists have found that the stalk of the flu virus mutates less than the head, and “conserves” more of its physical attributes year to year. And in recent years, they’ve developed the bioengineering technology needed to take a portion of that stalk, stick it on a molecule, and deliver it to the immune system in a way that convinces the body that it’s infected.
“So by targeting those conserved sites, we might be able to direct the body to generate an immune response to more than just the strains we’re exposing it to in the vaccine,” says Grace Chen, deputy chief of the NIH Clinical Trials Program.
The NIH vaccine was built using the stem of the flu strain called H1N1 — also known as swine flu — parts of which are already commonly used in traditional flu vaccines. In early trials in mice and ferrets, Chen’s group found that the vaccine induced immunity to at least one other strain — in particular, one that is known to have a high potential for sparking an epidemic. In future trials, they plan to incorporate a broader variety of strains, which should expand the vaccine’s coverage exponentially.
One of those volunteers is Michael Sonn, whose great-grandparents were among those killed by the 1918 flu when it struck Ireland. Sonn, who lives in Washington, D.C., says his grandfather was orphaned at the age of eight, and soon thereafter made a perilous solo journey to Brooklyn, where he grew up with an aunt and had a career operating subway trains.
His grandfather was a strong believer in the power of medical research, Sonn says, and his decision to participate in the universal flu trial was motivated by a desire to fight back against a disease that prematurely cut off a branch of his family tree. “The experience my family has had with the flu is a great motivator to me, personally,” he says. “And the idea of having a universal vaccine is personal to me. I really hope they’re on to something.”
Sonn received his shot over the summer and says that so far, there have been no side effects.
The NIH researchers caution that data from the trial won’t be ready until next year, and even then, subsequent trials with many more people will be needed before the vaccine could be publicly available, most likely well into the 2020s. But at a minimum, it should help confirm whether the innovative strategy behind the vaccine can work.
Even if it’s successful, the NIH vaccine likely won’t represent a permanent end to the flu. It will take years, maybe decades, to judge the vaccine’s longevity. It may be challenging to find a recipe of strains that will protect against not only seasonal human flu, but also the more dangerous varieties of flu that can jump from animals (think: bird flu). The vaccine’s effectiveness may also vary based on each person’s previous vaccination history (all of the people in the NIH trial got a normal flu shot within the last five years). And the NIH’s approach may have a higher risk of inflammation at the injection site, says James Cherry, a vaccine researcher at the University of California Los Angeles.
“Getting rid of flu forever is a tall order,” Pekosz says. “But anything that has stronger, broader protection is going to have a major impact.”
For Sonn, the trial participant, the question about participating in such a study was easy, and he has no regrets, only hope.
“He never had parents because of the flu,” Sonn says of his grandfather. “The potential to find a cure is so important. I’d do anything to support the research they’re doing now.”