The U.S. and other countries began industry-wide efforts to find a better vaccine, focusing on “acellular” formulas that used a few purified bacterial proteins to establish immunity rather than the whole cell, reducing the risk of inflammatory reactions. Researchers combined the new pertussis vaccine with vaccines against tetanus and diphtheria. DTaP, as it was known, was ready for the doctor's office in 1992. In the U.S., children receive it at two, four and six months; once between 15 and 18 months; and once between the ages of four and six, before they enter school.
From the start, public health authorities understood that an acellular vaccine might confer more temporary immunity than the problematic whole-cell vaccine. So, in 2005, they added a booster to the regimen to guarantee that children would be protected throughout adolescence. Officials determined the booster would be most effective for 11- to 12-year-olds but authorized it for use in any adult, eventually including pregnant women.
A Failure to Protect
After California's 2010 pertussis outbreak, additional outbreaks hit Wisconsin, Vermont and Washington, among other states, in 2012. Analyses of who was getting sick revealed the same pattern every time. Tom Clark, a physician and pertussis expert at the Centers for Disease Control and Prevention, describes it as a “striking stair-step appearance, rising by year: six, seven, eight, nine, 10 years old. If you go back several years [to when whole-cell vaccines were used], that stair-step is not there.”
The stair-step indicated that the more time elapsed since a child's most recent pertussis shot, the more likely the child would develop whooping cough after exposure to the bacteria. Many of these children were too young to have received their booster, so researchers hoped that once children got their additional shots, the unpredicted vulnerability would cease. New data from the Washington State outbreak quashed that hope: 13- and 14-year-olds were catching pertussis even after they received their booster shot. Other studies demonstrated that the vaccine was behaving differently from the older, reactive one: children who had received even one dose of the older, whole-cell formula while it was still on the market were better protected against pertussis than those who received only the newer vaccine. (Of course, children who received the new vaccine were still better off than those who had never been vaccinated.)
Clark points out that the original research on acellular vaccine in the 1980s tested whether it would protect but not for how long it would protect. Some diseases for which acellular vaccines are typically used, such as Hib meningitis, are only dangerous to children for a short time early in life, so long-lasting immunity is not necessary. Today, however, immunologists have better laboratory tools and a much more nuanced understanding of how immunity is evoked and sustained. “A lot of what you would do to develop a vaccine today was never done for the pertussis vaccine,” Clark says.
“The big answer is that we need a better vaccine,” says Mark Sawyer, a professor of clinical pediatrics at the University of California, San Diego, and chair of a working group collaborating with the Advisory Committee on Immunization Practices (ACIP), which helps to set federal vaccine policy. “But the ACIP can't just make that happen. That is up to the scientists who would do a study of what would make a better vaccine, and it is up to the pharmaceutical companies.”
If a new vaccine were formulated, demonstrating its superiority would be challenging. Every developed country vaccinates its children against pertussis, so there is no large unprotected population that could help prove a new vaccine's worth. And before encouraging manufacturers to consider developing a new vaccine, federal planners would have to weigh the unintended consequences of the endeavor. Diverting too much of the manufacturers' limited resources to one new vaccine could cause shortages of others, for example. Another concern is whether parents would heed the advice to bring children in for yet more shots.