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Study Finds Booster Vaccine Tdap is Only Moderately Effective

Researchers have found that the pertussis “booster” vaccine, also known as reduced antigen content acellular pertussis vaccine or Tdap, is only moderately effective at preventing pertussis among adolescents and adults. This is first study to assess the effectiveness of the Tdap booster in members of a new generation that has received entirely acellular vaccines appears in the current online issue of BMJ.

“The effectiveness of acellular pertussis or Tdap vaccines targeted toward adolescents and adults is not well understood, particularly among individuals who received acellular pertussis vaccines as children,” said lead author Roger Baxter, MD, co-director of the Kaiser Permanente Vaccine Study Center. “We found that acellular pertussis vaccines for adolescents and adults have only moderate effectiveness against laboratory-confirmed pertussis. While they provide protection, more effective vaccines may be necessary to prevent further outbreaks.”

Whole-cell pertussis vaccines, also called DTwP, were available from the 1940s to 1990s, but were associated with safety concerns that ultimately led to the development of acellular pertussis vaccines, which are also called DTaP. By the late 1990s, the United States had switched from whole-cell to acellular vaccines for all five recommended infant and childhood doses. Since 2005, the Advisory Committee on Immunization Practices has recommended boosting with Tdap for persons 11 years and older. However, studies to date provide little or no information as to the effectiveness of the Tdap booster when administered to the newly emerging cohort of adolescents previously vaccinated entirely with acelluar rather than whole-cell vaccines.

Despite high vaccine coverage in infants and children, since the 1980s the U.S. has experienced periodic outbreaks of pertussis, with incidence increasing over time. Although infants suffer most of the mortality from pertussis, adolescents and adults serve as reservoirs and vectors of infection and comprise about half of all cases. Reasons for the increase in pertussis are likely varied, but studies during recent outbreaks have found that acellular vaccines are less effective than earlier whole-cell formulations, and that protection wanes substantially after the last DTaP dose.

In 2010, pertussis incidence in California rose to its highest level in the past 50 years. With data from a six-year period including this outbreak, the Vaccine Study Center assessed the effectiveness of Tdap in reducing the risk of pertussis among adolescents and adults who had received DTwP vaccines, as well as among younger adolescents who had only ever received DTaP vaccines.

The study included all polymerase chain reaction (PCR)-confirmed cases of pertussis in Kaiser Permanente Northern California (KPNC) members aged 11 years and older from January 2006 to December 2011. The Tdap vaccination status of PCR-positive cases was compared with two control groups: persons testing PCR-negative for pertussis, and closely matched persons from the general KPNC population.

Using two different control groups, researchers found that Tdap vaccine effectiveness ranged from 53 to 64 percent. The study population included 668 PCR-positive cases, 10,098 PCR-negative controls, and 21,599 matched controls. Tdap vaccination rates were 24 percent in PCR-positive cases and nearly 32 percent in PCR-negative controls. The adjusted estimate of Tdap effectiveness against pertussis was 53 percent in the comparison with PCR controls, and 64 percent in the comparison with KPNC controls.

During the pertussis outbreak from January 2010 through June 2011, which includes nearly 75 percent of all cases in the study population, the incidence of pertussis in the entire KPNC population was strongly related to age. Incidence increased sharply after age 5, was highest at 10 and 11 years, then decreased sharply until age 15, and was low in adults.

Decreasing pertussis rates from ages 11 and up coincided both with the use of Tdap and with receipt of DTwP vaccines during infancy.  At the epidemic’s peak, Tdap vaccination rates were near zero percent until age 10, then rose rapidly reaching a high of 72 percent at age 15, then decreased to between 25–35 percent for ages 21-64, and to 10 percent for ages 65 and older.

In subgroup analyses, the Tdap booster was moderately effective both in older persons who had received all DTwP as infants and in younger persons who had received all DTaP. Yet, rates of pertussis were highest in the DTaP subgroup consisting of young adolescents ages 11-14, indicating DTaP protection waned substantially over time. As a result, the researchers noted, the absolute benefit of Tdap vaccination was much greater for DTaP than DTwP recipients. They added that strategies to decrease pertussis incidence should prioritize giving the Tdap booster to DTaP-only recipients, as California has done since the 2010 outbreak, requiring Tdap vaccination for middle school students.

“Our results reflect the average effectiveness of Tdap vaccination over all available follow-up time. We were not able to assess whether effectiveness waned over time because the vaccine is relatively new,” Baxter said. “But recent studies have found early waning of immunity for the childhood acellular pertussis vaccines, and future studies should examine whether there could be waning for the Tdap booster as well. Our findings draw attention to the need for more effective vaccines to prevent pertussis outbreaks.”

Additional authors on the study include Joan Bartlett, MPP, MPH; Ali Rowhani-Rahbar, MD, MPH; Bruce Fireman, MA; and Nicola P. Klein, MD, PhD, of the Kaiser Permanente Vaccine Study Center. This study was funded by Kaiser Permanente.

About the Kaiser Permanente Vaccine Study Center
Founded in 1985, the Kaiser Permanente Vaccine Study Center began as a way of responding to numerous requests to use Kaiser Permanente’s large population for vaccine efficacy studies. Key studies have focused on Haemophilus influenza, type B (Hib), chickenpox, pneumococcus, rotavirus and flu vaccines. The center operates 31 sites in Northern California and collaborates with Kaiser Permanente’s Northwest, Hawaii and Colorado regions, as well as participates in several Centers for Disease Control and Prevention and National Institutes of Health studies. For more information, visit www.dor.kaiser.org/external/DORExternal/vsc/index.aspx.

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