It's an annual autumn rite for many: trooping to the doctor's office or pharmacy for the jab that might stave off sniffles and aches during the flu season.
Scientists would love to make this ritual history, if only they could come up with a flu vaccine that would work for many years, instead of one. The problem is that influenza is a wily opponent — every year it wears a new disguise, foiling the body's immune system as well as the medical profession's attempts to stifle it. In designing the annual shot, scientists must guess what strain of influenza will be prevalent in the upcoming season.
Scientists around the world are working to craft a universal flu vaccine that would train the immune system to identify and destroy flu, no matter what type it is. The key is to make a vaccine using the unchanging parts of the virus — its Achilles' heel, says Dr. Antonio Lanzavecchia, an immunologist at ETH, the Swiss Federal Institute of Technology in Zurich.
That could happen by 2016, National Institutes of Health Director Francis Collins said in July.
A couple of companies have already tested their formulations in people. BiondVax Pharmaceuticals in Ness Ziona, Israel, is working on a vaccine that could be ready as early as 2014, predicts Wayne Rudolph, the company's vice president for corporate development. Seek, a drug development company in London, hopes to have a market-ready product in three to five years, says Chief Executive Gregory Stoloff.
Other scientists are more circumspect. "My prediction is 10 years before we see this in people," says Vincent Racaniello, a virologist at Columbia University in New York.
Recent events show that there's little time to waste. Pandemic flu caused by a type of H1N1 virus hit in 2009, and the United Nations announced in August that a new version of the deadly H5N1 bird flu is now circulating in Asia.
"It's almost inevitable that another pandemic will come," Lanzavecchia says.
The bird flu kills nearly 60% of those who get it, felling at least 332 people since 2003, according to the World Health Organization. The death toll remains low because people can pick up the virus only from a bird, not from each other. But if the virus gains the ability to jump from person to person, "it has the potential to decimate the world population," says Ian Wilson, a structural biologist at the Scripps Research Institute in La Jolla, who studies flu antibodies.
The influenza virus is studded with nail-shaped proteins, called hemagglutinin. The heads of those nails are flashy and constantly morphing. They distract the immune system and prevent it from seeing the less variable flu parts underneath, which might allow the body to recognize more than one kind of flu. Inside the virus are other variable proteins that disguise infected cells. The immune system tends to focus on these ever-changing parts.
Once exposed to a flu virus or vaccine, the immune system is primed to recognize it, usually via hemagglutinin's nail heads, and fight off that particular virus. The body makes antibodies that jam up the virus' works, preventing the intruder from entering or exiting cells. It produces killer immune cells that identify and destroy infected cells. And it remembers past diseases. You'll never get the exact same flu twice, but the problem is that there are near-infinite variations to contend with.
With flu strains constantly changing, people and the virus are locked in a perpetual "cat-and-mouse game," says Alan Shaw, chief scientific officer of VaxInnate Corp. in Cranbury, N.J., which has explored a universal vaccine in the past and is working to improve the seasonal vaccine.
Each winter, the WHO and the U.S. Food and Drug Administration must decide which three flu strains they think will be the most common in the next season. It takes six to eight months to manufacture the vaccine supply.
By the time flu season rolls around the following autumn, the three viruses in the vaccine might not be the right ones anymore. On average, the annual vaccine is 30% to 60% effective, Rudolph says.
To beat the flu at its own game, scientists have to focus the immune system's attention on the parts of flu that change little, if at all.
BiondVax chose nine unchanging pieces of the flu virus' proteins and linked them together — three copies each — like "a string of pearls," Rudolph says. These pieces teach the immune system to make antibodies and killer cells that will attack the virus, the company announced in June. Nearly 200 people have safely received the company's shot, and blood tests showed their immune systems responded to the vaccine.
Seek, for its part, has selected four pieces of the virus' internal machinery and designed them to match as many kinds of flu as possible.
About 40 people have received the Seek vaccine so far. In the latest trial, which Seek will present at the Influenza Congress in early November in Arlington, Va., 30 people received the universal flu shot and 30 others received an inactive placebo. Three weeks later, the scientists dribbled a liquid containing a mild flu virus into their noses.
The people who received the placebo came down with "proper flu symptoms," Stoloff says: fevers, sneezing and aches. Those who got the real vaccine suffered minimal effects. "They might just sneeze twice," Stoloff says. The researchers also discovered that the immune cells in the blood of vaccinated people attacked all kinds of flu viruses.
Scientists are entering the universal vaccine hunt with a variety of techniques. For example, Inovio Pharmaceuticals Inc. of Blue Bell, Pa., has invented a DNA-based vaccine. The company has shown that the vaccine protects animals from the flu.
And many researchers are working from blood samples of people who've already recovered from the flu. Very rarely they find in these samples an antibody that attacks many kinds of influenza. In July, Lanzavecchia and colleagues reported online in the journal Science that they'd found a human antibody that disables all flu.
Scientists like Lanzavecchia and Wilson hope that by understanding these natural multi-flu antibodies, researchers will be better able to design a universal flu vaccine. In the meantime, the antibodies could potentially be used to treat or prevent flu in high-risk populations such as elderly people or children.