Pertussis, better known as whooping cough, once sickened more than 100,000 Americans a year. The bacterial illness, which is particularly dangerous to infants, was brought under control in the 1940s with the introduction of pertussis vaccines. But in the past two decades pertussis has made an alarming comeback.

In 2012 the number of U.S. cases rose to 48,277—the most since 1955. The resurgence has led researchers to reexamine the workings of the current vaccine, which uses bits and pieces of the Bordetella pertussis bacterium to stimulate the production of antibodies. This so-called acellular pertussis (aP) vaccine is in the widely used DTaP and TdaP shots, which also protect against diphtheria and tetanus. An older formulation with whole, inactivated B. pertussis cells was phased out in the 1990s because of its side effects.

Recent studies have shown that immunity from the acellular vaccine wanes relatively quickly. In 2012, for instance, a New England Journal of Medicine study determined that children's odds of catching pertussis rose by 42 percent each year after receiving the final dose of DTaP, usually given between ages four and six, in the childhood vaccine series.

Tod Merkel and his colleagues at the U.S. Food and Drug Administration suspected another weakness lurked in the acellular vaccine—that it might not block the spread of the disease. To test their hypothesis, Merkel's team members infected baboons with pertussis. Some of the animals had been vaccinated, and some had acquired natural immunity from a past bout of the illness. None of the vaccinated or naturally immune baboons fell ill, but the bacterium lingered for 35 days in the throats of the baboons that had received the acellular vaccine. Animals that had received the whole-cell vaccine cleared the infection nearly twice as fast.

During their infections, acellular-vaccinated baboons were able to pass the bacterium to unprotected animals, Merkel's team recently reported in the Proceedings of the National Academy of Sciences USA. The study, says Eric Harvill, a professor of microbiology and infectious disease at Pennsylvania State University, “explains a lot of the observations about the circulation of pertussis in highly vaccinated populations.”

Finding out exactly how the different vaccines convey immunity might lead to a better pertussis shot, which Harvill, Merkel and their colleagues hope to develop over the next several years. “Clearly, the natural infection and whole-cell vaccine are stimulating some response besides the antibody response, and we're trying to find out what,” Merkel says.