The outbreak was the biggest in the U.S. since shortly before states began requiring a second shot for youngsters in 1990.
Nearly 6,600 people became sick with the mumps, mostly in eight Midwest states including Nebraska, and the hardest-hit group was college students ages 18 to 24. Of those in that group who knew whether they had been vaccinated, 84 percent had had two mumps shots, according to the study by the Centers for Disease Control and Prevention and state health departments.
That "two-dose vaccine failure" startled public health experts, who hadn't expected immunity to wane so soon - if at all.
The mumps virus involved was a relatively new strain in the U.S., not the one targeted by the vaccine, although there's evidence from outbreaks elsewhere the shots work well against the new strain.
The researchers, reporting in Thursday's New England Journal of Medicine, note the virus likely came from travelers or students from the United Kingdom, where mumps shots are voluntary and there was a much larger mumps outbreak of the same strain. Many countries don't vaccinate against mumps, so future cases brought from overseas are likely.
"If there's another outbreak, we would evaluate the potential benefit of a third dose to control the outbreak," said researcher Dr. Jane Seward, deputy director of the CDC's viral diseases division.
Mumps is spread by respiratory secretions and saliva among people in close contact, making college students particularly susceptible. Students' sharing of drinks and utensils, and sexual activity, probably increased their exposure.
Mumps causes fever and swollen salivary glands in the cheeks. Before the vaccine, complications such as deafness, viral meningitis and testicle inflammation, which can cause sterility, were common and there were a couple million U.S. cases a year.
The only U.S. vaccine, made by Whitehouse Station, N.J.-based Merck & Co., hasn't been changed since its introduction in 1967 and there are no plans to change it, said Barbara Kuter, Merck's executive director of pediatric affairs.
Over 500 million doses have been sold since the 1970s, when it was put in the combination measles-mumps-rubella shot.
Dr. John Bradley, a member of the American Academy of Pediatrics committee on infectious diseases, said his group is talking about possible changes to the vaccine recommendations schedule with CDC and other health agencies.
Now two shots are recommended, one at 12 to 15 months and the other at age 4 to 6.
It might not be cost effective to give everyone a third shot, but it should be considered for college students, said Dr. Stephen Marcella, an epidemiologist at University of Medicine and Dentistry of New Jersey's School of Public Health.
Dr. William Schaffner, head of preventive medicine at Vanderbilt University School of Medicine, said what's need is a longer-lasting shot.
"It's clear that over time, immunity wanes somewhat," he said. "We need a better vaccine."
Seward said other CDC studies on the 2006 outbreak found two mumps shots protected about 85 percent of people from the new strain - not quite enough to prevent spread even with the nearly 90 percent vaccination rate at the time.
The outbreak was in Illinois, Iowa, Kansas, Minnesota, Missouri, Nebraska, South Dakota and Wisconsin.