CURRENTS

April 16,
2007

Currents--University of Rochester newspaper

Scientist shares latest updates on flu research and the quest for a better vaccine

By Tom Rickey

Two weeks ago the University was awarded $26 million from the National Institute of Allergy and Infectious Diseases (NIAID) to establish the New York Influenza Center of Excellence. The center is part of a network recently established by NIAID to protect people against seasonal flu and future flu pandemics. David Topham, associate professor of microbiology and immunology and codirector of the influenza center, recently talked about flu and the role of the new center.

The flu’s been around a long time. Don’t we know enough about the flu already?

People think we know more about the flu than we do; it’s amazing how little we actually do know. The perception that flu is not a major threat is mistaken. Respiratory infections caused by bugs like the flu are the leading cause of death in many parts of the world, and it’s one of the leading causes of death and illness in the United States—35,000 people in this country die from flu each year and more than 200,000 people are hospitalized. It’s always been a threat.

We have a vaccine that works. What more is there to learn about flu vaccines?

The current vaccine does work, sort of. It works pretty well if scientists are correct in their predictions and match the vaccine to the strains of flu that will be prevalent in any given year. It works if millions of people get the new shot, year after year. It works if there is no major breakdown in the fragile manufacturing process. And, it works pretty well as long as the flu virus doesn’t mutate radically, allowing most people to carry some immunity forward year to year.

Even so, thousands die every year, and if the flu changes radically, millions of lives would be at risk immediately. The design and manufacture of flu vaccines has changed very little in the last three decades, yet our knowledge of the immune system has just exploded in that time frame. For instance, the best paper on the role of the body’s T-cells—the cells in the lungs that comprise our first line of defense against flu—was published more than 20 years ago, in 1983. Our knowledge has grown dramatically, but current vaccines haven’t kept pace. We aren’t tapping a crucial part of our body’s immune response in the fight against flu.

How did you become interested in the flu?

Before graduate school, I worked as a technician in a laboratory where we studied multiple sclerosis. There we looked at the idea that certain viruses might trigger MS, and we discovered a virus that can replicate in the central nervous system and cause paralysis. We ended up studying auto-reactive T cells, and that piqued my interest in viral immunology.

Was flu research as popular then as it is today?

Hardly! When I was a post-doc, I worked in the laboratory of Peter Doherty, a leading flu researcher at St. Jude Children’s Research Hospital. My friends asked me why I was spending my time studying the flu. “We have a vaccine, what else do we need to do?” they’d ask. But really, there were a lot of unanswered questions then, and there still are today. There are a lot of models of the immune system that focus on organisms that are really no threat to anyone. But flu claims tens of thousands of lives each year, and it offers a useful way to gain new insights into the immune system. It’s an actual human pathogen posing a very real threat.

What’s your specific research interest?

Here at Rochester, we have a specific strength in T-cell biology. T-cells in the lungs are our very first line of defense against the flu, fighting the virus in the first few days, until other parts of the immune system can gear up to respond effectively. When you first inhale a flu particle, you’re dependent on T-cells to fight off the virus. There have been huge developments in T-cell biology in the last few decades. But current flu vaccines don’t take T-cells into account very much. There are a lot of questions—for instance, why don’t your lungs keep enough of these cells around constantly to repel an infection like the flu? If you have to wait for these cells to become activated and travel to the lungs, that can take a couple of days, and for some infections, that’s already too late.

Where does your work with T-cells stand?

We’ve shown that having these T-cells in great numbers in the lungs, where they can move in quickly to attack the virus, provides better protection than having other cells ready to attack the virus in other parts of the body. And we’ve shown that being inoculated with a live flu virus, instead of the inactivated vaccine that is widely used, gives better immunity, and we think that’s because the live virus promotes the development of these T-cells. But we don’t understand the process completely. More of these cells in the lungs would help people fight off an infection – it could keep many people from becoming infected, and for those who are infected, they wouldn’t be as sick for as long. In a pandemic, they could keep you alive.

Just how likely is a pandemic from bird flu?

That’s impossible to say. Flu is unique because different forms of the virus can mix and match their genomes and create whole new strains. The more that a new strain that hasn’t been seen before, such as the H5N1 strain of bird flu, which by the way has killed more than half the people it has infected, spreads in birds and in people, the more likely that it will find itself in a person or animal also infected with another strain of flu. All it takes is for two forms of the virus in a single person to swap genes in the right way to create a new type of flu the world has never seen. If a new strain results, one as deadly as H5N1 but that passes from person to person as easily as the flu virus that sweeps through classrooms and hospitals every year, we’d have a pandemic on our hands.

Pandemic flu sounds like a looming threat. Has the threat been overlooked?

Well, you have to remember, we’ve had a vaccine against the flu, and the vaccine generally works great at protecting most people, under most circumstances. Flu doesn’t change radically all that often; in the last 100 years, it’s happened only three times. The last time flu took millions of lives was back in 1918, and not many people remember that. In addition, developing and manufacturing flu vaccine generally has not been lucrative for pharmaceutical companies. So there hasn’t been a great deal of incentive to work on new flu vaccines. However, when the flu virus changed dramatically into what became known as the Spanish flu of 1918, more than 50 million people lost their lives. And so far, the H5N1 form of bird flu is 20 to 50 times as deadly in the people it has infected. It would be irresponsible to ignore that threat. Remember SARS—people quarantined, planes grounded, people in cities like Toronto routinely wearing protective masks? SARS was a wake-up call. Bird flu would make SARS look like child’s play.

How might the research at the new center help protect us?

There are a number of ways. Some of the investigators will be studying how the flu actually spreads in families and in communities, and how different people’s immune systems respond to the vaccine. Again, you’d think we’d know more about this than we do. We’ll be following 150 families in the Rochester community for seven years, tracking their exposure to the flu and their responses to vaccination. In addition, much of our work will be on the basics of the immune system—the type of research that could ultimately result in the design of a much different, much more effective flu vaccine. It’s a bit like stepping back and exploring whole new ways of making a vaccine, instead of tweaking the tried-and-true methods that work well enough most of the time, but likely wouldn’t be effective in the face of a virulent new strain, such as H5N1, or against flu viruses that we simply can’t predict.

Why do you think Rochester was chosen for one of these Centers of Excellence?

My guess is that there are a number of reasons. We are a community with a strong history of tackling a broad array of complex issues related to vaccines. We have developed vaccines against childhood meningitis, and our technology helped bring about the first vaccine designed to prevent a form of cancer. Every year, millions of children across the nation receive shots that rely on technology developed at our university. In addition, we have incredibly strong surveillance of infectious disease in this community—we’re part of virtually every national effort to track disease and the effectiveness of vaccines. We have one of the highest rates of vaccination in the nation against a number of diseases.

We also have strong research in basic immunology, through the Department of Microbiology and Immunology and the David H. Smith Center for Vaccine Biology. And we have the Vaccine Treatment and Evaluation Unit, where Professor of Medicine John Treanor—who directs this new center—and colleagues test new vaccines against flu and bird flu, as well as diseases like anthrax, pneumonia, and whooping cough. That unit has led several national efforts to test bird flu vaccines, and spearheaded the nation’s response to make flu vaccine more broadly available after recent shortages. When you put it all together, it’s quite a combination that makes you think that we have as much a shot as any place of really contributing to protect the world against threats like flu and bird flu.

Tom Rickey is a senior science writer for the Medical Center Office of Public Relations and Communications. Read more about plans for the New York Influenza Center of Excellence at www.urmc.rochester.edu/pr/current_research/bird_flu/index.cfm.