Expert to Discuss Threat Posed by Flu, Efforts Toward New Vaccines

Nov. 11, 2009
Dr. David Topham
David Topham, Ph.D.

When microbiologist David Topham, Ph.D., began his studies on influenza 15 years ago, friends scoffed at his career choice, labeling influenza as “old news,” an unchallenging microbe that hardly posed a threat because a vaccine was available.

But his choice to hunt a bug that colleagues found uninteresting has thrust Topham into the middle of the first flu pandemic the world has seen in more than 40 years. Topham is an expert on how the body fights the flu, and he helps to direct a research center that is part of a key Federal network designed to fight the flu. He’s busy directing studies aimed at understanding the current pandemic and preventing future ones, as well as studying infected people to learn how the body fights the flu.

Topham will discuss his work on flu and the current pandemic at 4 p.m. this Friday, Nov. 13, in the Class of ’62 Auditorium (Room G-9425) at the Medical Center. The talk, part of the “Second Friday Science Social” lecture series, is geared mainly to faculty, staff and students at the University, though the general public is welcome as well.

The lecture comes at a time when the novel H1N1 virus, an amalgam of flu viruses from pigs, birds and people, just seems to be hitting its peak. Colleagues pass around hand sanitizer like candy, the new etiquette calls for actions such as coughing into one’s elbow, and doctors’ offices and hospitals brim with those ill from flu. And the normal “seasonal” flu season hasn’t even begun yet.

of this is a shock to Topham, who cut his teeth doing research as a post-doctoral associate in the laboratory of Nobel Prize-winning flu researcher Peter Doherty at St. Jude’s Children Hospital.

“A flu pandemic like this one is certainly no surprise,” said Topham, an associate professor of Microbiology and Immunology. “Flu is a human pathogen that poses a very real threat. There are a great number of unanswered questions – really, more questions than answers. Respiratory infections caused by bugs like the flu are one of the leading causes of death and illness in this nation.”

The flu’s ability to mix and match bits and pieces of different viruses to create new ones is at the heart of what makes the bug such a challenge. Usually, the virus changes a little bit from year to year – enough to require a new flu shot each year to prevent infection but not so much to be a global threat. But once every few decades, the virus changes in such a fundamental way that a true global epidemic, or pandemic, occurs.

In recent years, the so-called bird flu – H5N1 – gained a lot of headlines, mainly because of its incredible mortality rate. H5N1 is at least 20 times as lethal as the Spanish flu of 1918, which killed more than 50 million people worldwide. But H5N1 hasn’t gained the ability to pass easily from person to person.

Then earlier this year H5N1 was eclipsed by novel H1N1, a new flu combination that doesn’t appear much more lethal than the seasonal flu but which is far more contagious, because many people have very little or no immunity to it. The focus of researchers quickly switched from bird flu to swine flu. (Luckily, no strain has emerged equipped with both the lethality of H5N1and the transmissibility of H1N1.)

The pandemic comes two years after the creation of the New York Influenza Center of Excellence, one of five flu research centers created by the National Institutes of Health to help the nation prepare for a flu pandemic. The creation of the centers is one of several steps that Topham cites as crucial for allowing the nation to be as prepared as it is for pandemics like the current one. While many people gripe about the delay in receiving the new flu vaccine, Topham says it’s only because of careful planning that there is vaccine at all.

“If this pandemic had occurred 10 years ago, it is likely there wouldn’t have been any vaccine for H1N1 available in time for this year’s flu season,” said Topham, who is co-director of the center. “We’ve been preparing for a scenario like this for several years – outfitting more facilities to produce vaccine, boosting research against the flu.

“Efforts in response to H1N1 have really been rapid and dramatic, including steps to recognize a new type of flu, isolate it, sequence it, and then develop a vaccine and produce enough to protect millions of people. People at the National Institute of Allergy and Infectious Diseases saw this coming and invested the resources necessary to be prepared. It was great planning.”

At the center Topham and John Treanor, M.D., are conducting a flu surveillance study involving more than 100 families and more than 80 college students so far. The idea is to track participants closely to understand how the flu can move through a community, and to apply today’s sophisticated laboratory techniques to look at the immune systems of people infected with flu. Already the study has been going on for two years, giving scientists great baseline data on how the immune system functions even before a brand new flu virus enters the scene.

The center is also particularly strong in basic research into the body’s defenses against flu. Topham himself is an expert on T cells, a type of immune cell that kills menacing cells such as those that have been hijacked by viruses to produce viral particles by the billions. 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. But current flu vaccines don’t draw much on T cells, Topham says. He is studying ways to involve T cells more directly in the fight against flu. 

T cells also offer some unique opportunities for creating a flu vaccine that would protect against many types of flu, a key step toward a type of “universal flu shot” that could make the yearly flu shot – or the panic over a new flu strain – a relic of the past. But such a possibility is a long ways off, Topham says, adding that there is not a lot of data – yet – to guide researchers seeking to boost how the human body actually fights off the flu.