How Far Off Is a Better Flu Shot?

Someday you may only have to get a flu shot every five years.

As you waited in line for your flu shot last weekend, you may have been wondering: Why must I go through this every year?

The answer is that the influenza virus is a slippery character. Some viruses barely change at all over time. The measles virus, for example, is "as stable as stone," said William Schaffner, chairman of the department of preventive medicine at Vanderbilt University.

Chicken pox, too, is consistent from year to year. But influenza is "genetically plastic," said Schaffner. It mutates all the time, and it can combine with other flu strains to regularly make new variants.

Those kinds of changes happen so frequently that the body's immune system won't necessarily recognize this year's iteration of the flu as a dangerous threat—even if you suffered from or were vaccinated against last year's version.

"It's like putting on a new sport coat every winter," said Schaffner, the past president of the National Foundation for Infectious Diseases.

The vaccine has to be updated every year to account for the flu's changes. But forecasting what those changes will be is tough.

Every year, public health officials try to predict the three flu strains—two of influenza A and one of influenza B—that will be common in the coming winter. They do this months in advance, giving manufacturers time to produce, distribute, and administer the vaccine.

"Here you are in March, trying to figure out what will be circulating next February," said Schaffner.

In the intervening months, circulating strains of the flu virus can change enough to reduce the vaccine's effectiveness.

Even when the seasonal vaccine is a good match, it doesn't offer complete protection. People may be infected by a less common strain not included in the vaccine.

Some, especially the elderly, very young, or those with certain health conditions, don't develop a strong immune response to the flu even after vaccination. Others get exposed to the flu before the vaccine can take effect.

The Centers for Disease Control and Prevention last week estimated the effectiveness of this year's vaccine to be 62 percent, based on a one-month survey of more than a thousand adults and kids.

That's in line with the historical average. A 2011 review of previous research published in Lancet Infectious Diseases found that vaccines had a combined efficacy of 59 percent against flu in healthy adults aged 65 and younger.

Trying to Change the Game

That less than stellar record has scientists working to develop better tools to fight flu.

"Is [the current vaccine] the answer for tomorrow? Yes, it's the best we have. Use it," said Michael Osterholm, lead author of the 2011 review and director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

"Is this the answer for the next few tomorrows?" he continues. "No. We need better flu vaccines."

And that need is acute. The World Health Organization puts the global death toll from seasonal flu at 250,000 to 500,000 per year, out of 3 million to 5 million severe cases. In the United States, an estimated 3,000 to 49,000 people die each year from the flu, according to the CDC.

Osterholm was the lead author of an October Center for Infectious Disease Research and Policy report that called for "game-changing" influenza vaccines.

The traditional flu vaccine includes pieces of the "head" of the hemagglutinin protein, which is found on the surface of the flu virus. When immune cells called B cells run into those bits of protein after vaccination, the cells learn to make antibodies against them. Later, if the actual flu virus comes along, these prepared B cells can mount a speedy response and prevent infection.

The problem is that this part of hemagglutinin mutates rapidly, and the older antibodies are of no use against the newer version of the virus.

Researchers and some biotech companies are now trying to target proteins in the influenza virus that don't vary from strain to strain and from year to year.

"If this piece of the virus is the same among all influenza viruses and doesn't change over time, maybe we can make a vaccine against it," said Gregory Poland, director of the Mayo Clinic's Vaccine Research Group.

The hope is that the approach yields a universal vaccine that protects against seasonal flu without annual shots. Such a vaccine could also keep the body poised to fend off a major new flu virus, like the 1918 strain that killed tens of millions of people and the 2009 pandemic of a strain of H1N1, aka swine flu.

As they seek that silver bullet, researchers are taking a variety of approaches.

Sarah Gilbert, a professor of vaccinology at the University of Oxford, is working with colleagues on a vaccine that interacts with the body's T cells, which kill other cells that have been infected by a virus.

"T cells can recognize human cells infected with the virus because very small regions of the [infected cells'] contents are displayed on the outside," said Gilbert. "It's like putting little flags on the outside to say there is something nonhuman inside."

The advantage is that those little flags on the outside of infected cells don't vary much from flu strain to flu strain.

The Wait Continues

The Oxford group has published the results from some small, early studies in humans but will need many more studies to prove T cell approach is effective, Gilbert said.

Even if that or other new vaccines make it to market, the likelihood of a flu shot for life is low. Immunity declines over time, so people would probably need boosters.

"I think we'll probably move to a shot every five years," said Gilbert. Such a shot could be offered year-round, cutting down on lines at drugstores and doctors' offices between September and March.

For now, the wait continues. "Candidate vaccines are in early trials," said the Mayo Clinic's Poland. "It could be four to ten years before we see one."

The Center for Infectious Disease Research and Policy report from October noted that it can take as long as 15 years and as much as $1 billion to bring a new vaccine to market.

It also predicted that flu vaccines taking an entirely new approach will face a longer approval process and "substantially higher" financial risk than more traditional vaccines. More studies will be needed, and regulators will need to figure out, for example, how to estimate the biological effectiveness of a vaccine that doesn't rely on the same mechanism as today's vaccines.

The October report urged changes to the U.S. government's regulatory process for approving new flu vaccines and "coordinated partnerships involving national governments, the pharmaceutical industry, the investment community, and academia." And it called on the U.S. government to "assume a primary leadership role" in spurring the development of new vaccines.

Can't wait for all that? There is an incremental improvement to the current flu vaccine coming soon.

Starting in the 2013-14 flu season, there will be a "quadrivalent" vaccine available that will protect against two influenza A and two influenza B strains. In a couple of years, all vaccine manufacturers will be making them, said Poland.

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