Published online 30 July 2008 | Nature 454, 565-569 (2008) | doi:10.1038/454565a

News Feature

HIV: The next shot

Researchers trying to develop an HIV vaccine have endured two decades of setbacks. Erika Check Hayden meets a veteran still engaged in the fight — and a rookie willing to join in anyway.

Larry Corey (left) and Colleen Doyle.D. FORBES/FRED HUTCHINSON CANCER RESEARCH CENTER; K. FUNG

As Larry Corey boarded a plane on the night of 18 September 2007, he was in shock. For four years, he had been in charge of clinical trials of a vaccine against HIV. Although previous vaccines had failed, Corey was optimistic that this one might work because it took a new approach. He thought it was the best hope against HIV. But that afternoon, Corey had met with scientists who had reviewed the early trial results. Not only did the vaccine not work, they told him, it might actually have made some people in the trial, called the STEP Study, more vulnerable to infection.

On the long flight from Chicago home to Seattle that night, Corey cycled through stages of grief, regret and resolve. He had led the search for an HIV vaccine since its inception more than two decades ago. Now, as head of the flagship HIV Vaccine Trials Network run by the US National Institutes of Health (NIH), Corey had to make some difficult decisions. He had to decide what to tell the trial volunteers, and he had to think about the millions of other people who might contract HIV in the future. What could be done to make the vaccine that they so desperately needed?

As Corey pondered these issues, another HIV researcher was mulling over a decision of her own. Colleen Doyle is 32 years younger than Corey and had earned her PhD only three months before. Yet she had just received a job offer from the University of Chicago. The position was a rare and precious opportunity for such a young scientist. But there was a catch: if she took the job, she would have to stop her investigations of how a vaccine could arm the body against HIV.

Both Corey and Doyle had reached turning points, and their decisions could prove crucial to the search for a vaccine. The disappointing failure of the STEP trial marked one of the most difficult moments in HIV vaccine history. It told Corey and other scientists that after decades of work, they still did not understand how to prevent HIV from overwhelming the immune system. And critics were calling for an end to the vaccine hunt, so that some of the money — more than US$900 million was spent last year (see graph) — could go towards drug treatments.

But where some see an end to the field, Corey and other researchers see a new beginning. They say that basic research will eventually answer the outstanding questions about HIV, if talented researchers like Doyle can be coaxed into the fight. "We need a period of solid, quiet science, even if it takes a decade," says virologist and long-time HIV vaccine researcher John Moore from Weill Cornell Medical College in New York.

With this resolution, veteran vaccine researchers are facing a new reality: they will not be the ones to end HIV. They must now pass the baton to a new generation of scientists. "The real next step is going to come from outside this room," declared Adel Mahmoud of Princeton University in New Jersey, at an HIV vaccine summit this March in Bethesda, Maryland. But Doyle had watched the first generation of vaccine hunters endure decades of frustration. So the question she faced last September was, did she really want to heed that call?

“All of a sudden we had this fatal illness, and we were pretty impotent against it.”

Larry Corey

Born in 1947, Corey grew up in Detroit and decided at age 10 to become a doctor. As an undergraduate at the University of Michigan in Ann Arbor, Corey started dating Amy Glasser, whose dad had just finished supervising the field trials of the Salk polio vaccine. So when Amy and Larry were married in 1969, Jonas Salk was a guest at their wedding. No one foresaw that Corey would one day emulate Salk's quest to vaccinate humanity against a terrifying viral scourge; at the time, Larry was leaning towards cardiology.

That changed in 1975, when Corey began a fellowship with King Holmes, an expert in sexually transmitted infections at the University of Washington in Seattle, and discovered that he loved research. "That moment of discovery is a wonderful thing," he says, sitting in his office decades later at the Fred Hutchinson Cancer Research Center in Seattle. Now a lanky, grey-haired 61-year-old 

Erika Check Hayden is a senior reporter for Nature based in San Francisco. See Editorial, page 551.

  • References

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