In its own day, the chicken-egg flu vaccine was a headline-grabbing triumph. Medical researchers first started looking for a flu vaccine during the carnage of the 1918 pandemic. But all attempts to create one failed, and for a very simple reason: no one knew what caused influenza. It wasn’t until 1933 that British researchers first isolated a strain of the virus.
Scientists had discovered that they could create an abundant supply of viruses to study by injecting them into chicken eggs, and flu researchers started doing the same. As scientists came to understand the biology of the flu virus better, they started testing egg-grown viruses as vaccines. Injected into people’s arms, the vaccine viruses, doused with chemicals to inactivate them, triggered a protective immune response. The U.S. military took over flu-vaccine research during World War II, fearing that a 1918-scale pandemic would paralyze the Army. In 1943, American soldiers rolled up their sleeves and started getting an early flu shot.
The flu vaccine raised hopes that deadly pandemics would become a thing of the past. But it proved to be remarkably fickle. Vaccines for other diseases typically protected people for decades—even for life. The flu vaccine’s protection could abruptly fade away.
The reason for this failure, it would turn out, is that flu viruses are especially good at evading vaccines. When we get a flu vaccine, our immune system responds by making antibodies. Later, if we get infected by a flu virus, the antibodies attack it. Most of the antibodies will latch on to the tips of proteins that stud the surface of the virus, interfering with the virus as it tries to invade our cells.
But a flu virus mutates at an exceptionally high rate as it reproduces, and some mutations will change the tips of the surface proteins. The antibodies cannot grab tightly to the altered tips, so the virus is able to proceed with its invasion. From one flu season to the next, the evolution of the flu renders last season’s vaccine useless. The only way to protect people against a new year’s flu is to give them a new vaccine. On a chart of vaccine schedules, the flu vaccine’s stands out as the only one that requires annual injections. “There’s really nothing else like it,” says Richard Webby, a virologist at St. Jude Children’s Research Hospital in Memphis, Tennessee.
The World Health Organization monitors flu strains as they rise to dominance, and each February it convenes a meeting to recommend which strains should go into the vaccine for the next flu season in the Northern Hemisphere. In September, it meets again to make the same decision for the Southern Hemisphere.
There are many ways for a year’s vaccine production to go wrong. The vaccine may turn out to work worse than expected. When scientists adapt viruses to grow better in eggs, the viruses mutate in ways that are not possible in viruses outside the lab. The viruses that go into a vaccine can thus provoke antibodies that are mismatched with the viruses it’s supposed to fight. In some years, the eggs themselves become infected with pathogens, wiping out millions of doses.