Flu Breakthrough: The Search for a Universal Vaccine

Tired of having to get a different flu shot -- or two -- every year? Someday one shot may protect us against all the strains.

From the WebMD Archives

Medical sleuths have been trailing the elusive cold and flu viruses for more than a century. Now they finally might be onto something. A universal flu vaccine could be on the horizon -- and even more effective treatments for the common cold. Wayne Marasco, MD, PhD, is one of the most ardent sleuths. His perp -- the flu virus -- has caused the deaths of more than 36,000 Americans, and that’s just in one year.

Marasco is an associate professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical School. His work means that a universal flu vaccine could be within reach -- one that would protect against all flu strains over a lifetime, just like existing vaccinations for diseases like measles and smallpox. Up to now, a universal flu vaccine has been elusive, because the virus's constant ability to change has made it a hard target to combat. "The virus undergoes a process we call antigenic drift, which means that it continuously evolves so that it escapes the immune system," he explains. "We've been kind of chasing our tails and immunizing every season to keep up with these variations."

Even though only two different types of flu virus -- A and B -- are responsible for most human flu cases, each type has several subtypes, and the virus can change from season to season. That's why researchers can never seem to keep up.

The 1918 Flu Pandemic

Compounding the problem is that people are always on the move. Hundreds of years ago, Europeans first carried the flu to North America on ships, infecting Native Americans who had previously been flu-free. Today, air travel can speed flu viruses (including the H1N1, or swine, flu) around the world even faster. Last year swine flu was reported for the very first time among the Matsigenka tribe deep in the Amazon jungle, proving that no place is too remote to escape a flu bug.

Even before the age of commercial air travel, the flu virus was able to get around. In 1918, after the influenza A virus jumped from birds to humans, soldiers in World War I spread the disease as they moved around the European front. By the time the worldwide pandemic had ended a year later, a quarter of Americans had become sick and 50 million people worldwide had died from the illness, which was named the Spanish flu.

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Researchers have since discovered one reason the 1918 flu strain was so lethal. Unlike most of today's flu viruses, which can only copy themselves in the upper respiratory system (mouth, nose, and throat), the Spanish flu was able to replicate inside the lungs. As infected peoples' lungs filled with fluid, they suffocated to death, sometimes within a day or two of showing symptoms. While the H1N1 swine flu virus is also able to directly infect the lungs, researchers note that so far it has not been nearly as deadly as the Spanish flu.

Recently, researchers have discovered something else about that 1918 strain -- it's the genetic granddaddy of the H1N1 flu strain that's making headlines today. They traced the 2009 H1N1 virus back to the 1918 Cedar Rapids Swine Show in Iowa, where many pigs developed a respiratory infection that looked an awful lot like the influenza virus that was spreading like wildfire among humans. Over the next 90 years, that virus swapped genes a few times with other flu viruses, and re-emerged as the H1N1 flu strain we're dealing with today. The H1N1 flu strain circulating now is nowhere near as lethal as its predecessor, but unlike the H1N1 flu, it tends to be more dangerous to young people, and researchers think they've figured out why. Older people (particularly those born before 1950) have been exposed to the swine flu's relatives, and their bodies have built up antibodies to the virus. Young people don't have that same immunity.

The History of the Flu Shot

The 1918 pandemic was particularly vexing to doctors because they had nothing at their disposal to prevent or treat it. Researchers didn't even discover the influenza virus until 1933, and a working vaccine wasn't released until a decade later. Even today, with 21st century medical technology at our disposal, flu vaccination involves a lot of guesswork and uncertainty. Researchers from around the world have to look at flu surveillance reports several months in advance, anticipate which strain will be prevalent in the coming season, and hope their prediction is correct. They still haven't been able to create one vaccine that can target all strains for all seasons.

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But that might be about to change.

Last spring, Marasco made a huge breakthrough -- he finally hit on the flu virus's weakness. On the virus's surface sits a lollipop-shaped protein called hemagglutinin, which enables it to break into human cells and make us sick. Current flu vaccines trigger the immune system to launch an antibody attack against the most obvious target on that lollipop -- the big head at the top -- but that head is able to continually change and evade attack. Marasco has discovered human antibodies that instead target the stalk of the hemagglutinin protein, which is less likely to change and stays constant in different flu strains.

So far, the antibodies he's discovered have neutralized most flu strains tested. The next step is to get a drug based on these antibodies into clinical trials, which could happen as early as 2011, he says. If all goes well, Marasco's discovery could lead to the very first universal and long-lasting flu vaccine -- and the end of the seasonal flu shot ritual.

The Search for a Cold Cure

Meanwhile, in a laboratory at the University of Maryland School of Medicine, medicine and physiology professor Stephen B. Liggett, MD, is trying to crack the case of another public nuisance: the common cold. Doctors have been trying to cure this menace for almost as long as people have been getting colds, which is as far back as anyone can remember.

Trying to understand what makes all of the cold virus strains tick has not been easy. For Liggett and his research team, it was a meticulous and time-consuming task to sequence the genome of nearly 100 different strains of human rhinovirus -- the virus responsible for most colds. Decoding the 7,500 DNA bases that make up each strain is helping them understand the virus's design, family history, and vulnerabilities.

What Liggett's team has learned is that many cold viruses are related. On the rhinovirus family tree are about 10 groups of closely related viruses. That's good news, because it means that antiviral drugs could potentially be developed to target families of viruses, rather than trying to treat each individual strain. The bad news is that if two different cold virus strains infect the same person with a cold, they can swap genetic material to make a new strain. This means each cold virus has the potential to quickly produce new strains.

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The question Liggett is trying to answer now is whether the viral strains he's analyzed evolved many years ago, or whether repeated combining of DNA -- called recombination -- by various strains is causing new ones to keep popping up all the time. "If it freely recombined and we know that people can be infected with two viruses at one time, there would be an almost infinite number of strains. That would be a bad thing," he says.

Liggett has made great strides, but he admits there is still a lot to learn about the cold virus, such as how the virus varies from person to person and from season to season, and which strains are most virulent.

His next step is to do more extensive DNA analysis on rhinoviruses taken from 3,000 people to determine which group or groups of viruses might be worth pursuing for new therapies. If he's able to figure out which strains are coming back from year to year, and why some virus strains are more infectious than others, Liggett is hopeful that highly effective cold treatments might one day be a reality.

That day might be a long time coming, though. Some experts, including Ronald Eccles of the Common Cold Centre at Cardiff University in Wales, think the common cold is one nuisance we might never be able to shake. "We may be able to control some of these viruses," Eccles says, "but I believe that as long as we have noses, there will be viruses that cause colds."

Myths About the Common Cold

There's still a lot of folk wisdom circulating about the common cold -- some of which is true and some of which is not.

Chicken soup. Grandma was pretty close on this one. So-called Jewish penicillin slows the activity of immune substances that stimulate mucus production, helping clear up stuffy noses and coughs. Other cold-fighting nutritional remedies include a hot drink, or even a hot pepper, to soothe a sore throat.

Touch-and-go. Do cold viruses actually live on surfaces? Yes -- the rhinovirus can linger on countertops, door handles, and other frequently touched surfaces for hours after being touched by someone with a cold. If you’re the next person to touch one of those surfaces and you put your fingers in your eyes, nose, or mouth, you could be in for a nasty infection.

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"C" for colds. Vitamin C was once touted as the cure-all for the common cold, but the research just doesn’t hold up. It might slightly shorten and weaken colds, but vitamin C won't stop you from getting sick in the first place, and large doses can cause side effects like upset stomach.

Feed a cold. The first part of this old wives' tale might have some truth to it. A Dutch study found some evidence that eating a meal boosts the immune response needed to fight off the cold virus. And no, you don't want to starve a flu. Plus, it's especially important to get fluids.

Remedy reality. Can echinacea and zinc cold remedies help you avoid a cold? The evidence is mixed, but overall, research doesn't support the use of either for the prevention of colds. And steer clear of zinc nasal products; the FDA warns they might permanently reduce your sense of smell.

WebMD Magazine - Feature Reviewed by Michael W. Smith, MD on December 23, 2009

Sources

SOURCES:

Wayne Marasco, MD, associate professor of medicine, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Cambridge, Mass.

Stephen B. Liggett, MD, professor of medicine and physiology; director of Cardiopulmonary Genomics Program, University of Maryland School of Medicine, Baltimore.

Ronald Eccles, director, Common Cold Centre, Cardiff School of Biosciences, Cardiff University, Wales.

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