The most vexing thing about the annual flu vaccination is that it’s annual.

You have to get it every year, and many people don’t do so. In fact, the Centers for Disease Control and Prevention recently reported that only 2 out of 5 Americans have received the shot so far this flu season.

Wouldn’t it be easier if a flu shot were a once-in-a-lifetime event, or even once or twice in a decade? Public health officials see that as a potential game-changer.

“If we had an effective universal vaccine, it would take a huge dent out of health-care costs [and] disruption of work, school attendance and social activities,” says William Schaffner, a professor of medicine at Vanderbilt University and medical director of the National Foundation for Infectious Diseases. “It could change the entire way we prevent influenza.”

The idea no longer seems so elusive, says Barney Graham, deputy director of the vaccine research center at the National Institute of Allergy and Infectious Diseases. Modern molecular technology enables scientists “to design things at atomic resolution,” which “really wasn’t possible until the last few years,” says Graham, who is trying to develop what scientists call a universal, or long-lasting, vaccine.

Several groups of scientists, including Graham’s, have reported progress toward a vaccine that could protect against flu permanently with a single injection or with a shot given every five to 10 years.

Either approach would be a big advance over current practice, which requires health officials to predict major flu viruses nine months in advance so manufacturers can adjust the vaccine each year. With a universal vaccine, “we wouldn’t have to worry about that,” Schaffner says. “Each year we could go after people who hadn’t been vaccinated before. It could be a year-long, daily vaccination activity, not just focused in the fall.”

The hope is that such a broad-spectrum vaccine also could protect against rare but potentially deadly pandemics. “It would be the single most important thing we can do in public health today,” says Michael Osterholm, a professor of public health and the director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

While flu can strike anyone, it is most dangerous for the very young, the elderly and the chronically ill. Globally, seasonal flu epidemics produce 3 million to 5 million cases of serious disease every year, resulting in 250,000 to 500,000 deaths, according to the World Health Organization.

Symptoms include fever, dry cough, headache, muscle and joint pain, severe malaise, sore throat and runny nose.

The two major types of seasonal influenza viruses that can infect humans are A and B. Type A viruses, which are constantly changing, are the ones usually responsible for yearly epidemics. Scientists classify type A viruses into subtypes based on the combinations of the two molecules that cover the surface of the virus, hemagglutinin and neuraminidase.

Vaccines work by stimulating the production of antibodies against pieces of the virus. A universal vaccine would need to provoke antibodies that bind to “conserved” regions of the virus — that is, areas that stay the same and are common to most flu viruses. Currently, seasonal vaccines are designed to respond to the hemagglutinin head, which changes every year.

(Monica Akhtar/The Washington Post)

Researchers are using different strategies that target the common areas.

Two groups working separately, for example, are focusing on hemagglutinin’s stem, or stalk, which, unlike the head, doesn’t change. To do so, each team had to first figure out how to stabilize the stalk after lopping off the head. (The head is removed because it draws key immune system cells — those needed to make antibodies — away from the stem.) Each using a different approach, the teams have found a way to anchor the stem once the head is eliminated.

Another team built an entirely new virus in the lab by using recombinant DNA techniques, then designed a vaccine based on its conserved elements. “We hope that by doing that, our immune system will remember the conserved regions . . . so that changes in the head won’t matter,’’ says Peter Palese, chair of the microbiology department at the Icahn School of Medicine at Mount Sinai in New York.

Finally, another group has developed an experimental multiyear vaccine based on the genetic sequences of flu strains that have appeared in the past century. These researchers believe it is unrealistic to assume that any experimental vaccines, including theirs, will last a lifetime without requiring an update; thus, they are reluctant to predict the effectiveness of their own beyond five to 10 years — but even that would be an improvement over having to get an annual shot.

“We can go back in history and make vaccines that protect against all the variants for the last 100 years,’’ says Ted Ross, director of the Center for Vaccines and Immunology at the University of Georgia’s College of Veterinary Medicine. “That doesn’t mean we can do 100 years in the future, but we still can prevent a lot of disease. We just don’t know when and if one approach will have longer staying power than another. We’ll find out.”

While animal studies of various prospective vaccines are promising, it probably will be years before researchers start testing them in humans. Still, public health officials are excited. The idea of a universal vaccine seemed a pipe dream until recently. “But now, or very soon, it may no longer be a flight of fancy,” Schaffner says. “Some very impressive scientific efforts are underway to make this real.’”