Young Innovator Profile: John Wherry

As a child, John Wherry enjoyed taking apart machines, including his father's treasured toy train. Now, as an immunologist, he's dismantling perhaps the most intricate machine of all — the human immune system — to develop a vaccine that provides lifelong immunity against influenza. There's no time to waste, given the threat of a global pandemic triggered by mutations in the deadly bird flu virus that have emerged in Asia, Africa, and Europe. Wherry and co-workers are racing to create a prototype for the vaccine by 2011.

Wherry, 36, knew by high school that he wanted to be a biologist. During college, he became fascinated with immunology, and went on to study memory T cells as a graduate student. During a postdoctoral fellowship, he helped discover why some memory T cells, after being activated by an infection or vaccination, grow weaker: they sprout a receptor that blocks a signal telling them to fight.

The drawback of current flu vaccines is evident every fall and winter when people have to line up for a flu shot. Current vaccines typically use killed or inactivated flu viruses to stimulate the immune system to generate antibodies against proteins on the surface of those viruses; the antibodies recognize the virus as an invader and clear it from the bloodstream. But because two or three different influenza virus strains are usually circulating around the world at any time, and because their external proteins evolve rapidly, public health specialists have to formulate new flu vaccines every year.

Wherry, based at the Wistar Institute in Philadelphia, Pennsylvania, hopes to overcome those problems with a vaccine made in part from a live virus — a disabled common cold virus with pieces of cloned flu virus inserted into it. In theory, it will stimulate a deep, long-lasting defense called cellular immunity, which involves something called a memory T cell, a kind of white blood cell partially formed in the thymus gland in response to a foreign virus or bacterium. Unlike current vaccines, a T cell reacts to the stable proteins inside an influenza virus, as well as to its ever-changing surface proteins. And once a T cell has formed, it perpetuates itself for generations. Unlike antibodies, T cells are capable of destroying cells that have been invaded and colonized by viruses.

"If we can train the T cells to effectively recognize the internal proteins for influenza virus and be maintained long term," Wherry says, "it might be possible to create a vaccine that protects against all strains of flu. We're enthusiastic," he says. "We're starting to see promising hints in mice. But translating these things to humans takes a tremendous amount of time and effort."

"Eighty percent of these approaches fall flat," says Wistar's immunology chief, Hildegund Ertl. "Some people get discouraged by failure. What has impressed me about John is not only that he is a good scientist, he also clearly has the temperament to deal with setbacks."

This article is excerpted from "Flu Fighter" by Arthur Allen, which originally appeared in SMITHSONIAN, October 2007. Arthur Allen, of Washington, D.C., is the author of Vaccine: The Controversial Story of Medicine's Greatest Lifesaver.

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