Waning Immunity to Tdap Vaccine in Adolescents

Veronica Hackethal, MD

May 04, 2015

The effectiveness of the Tdap vaccine for pertussis decreases substantially among adolescents after 2 to 4 years, according to a study conducted in Washington State and published online May 4 in Pediatrics.

"We have found that among adolescent recipients of all acellular vaccines, overall Tdap [vaccine effectiveness] is 64%, with substantial waning of protection after 2 years," write Anna Acosta, MD, from the Epidemic Intelligence Service, Scientific Education and Professional Development Program Office, and the Meningitis and Vaccine Preventable Disease Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, and colleagues.

"[T]his waning is likely contributing to the increase in pertussis among adolescents," they add.

After 1997, acellular pertussis vaccine, which is commonly given in five doses during childhood, began to replace the previous DTP (diphtheria, pertussis, and tetanus) vaccine.

Recent events have raised concerns about waning immunity to Tdap vaccines, especially among adolescents, compared with DTP, which included a whole-cell pertussis vaccine. In 2012, more than 48,000 pertussis cases were reported in the United States, which is more than any number reported since 1955. In that same year, Washington state experienced a pertussis epidemic involving almost 5000 cases. A surprisingly high number of adolescents aged 13 to 14 years contracted the disease, even though 86% of this age group had received the Tdap vaccine.

The current case-control study looked at the effectiveness and duration of immunity conferred by Tdap among the first cohort of adolescents who received acellular vaccines in Washington state. The study included all pertussis cases reported in seven counties from January to June 2012 among adolescents aged 11 to 19 years. Researchers matched cases to three controls randomly selected from primary care clinics and matched to birth year. They identified vaccination histories using medical records, the Washington State Immunization Information System, and parent interviews. They also classified cases on the basis of type of vaccine and birth year: either a mix of whole-cell and acellular vaccines (1993-1997) or all acellular vaccines (1998-2000).

Among adolescents who received all acellular vaccines (450 cases, 1246 controls), overall effectiveness of the Tdap vaccine was 63.9% (95% confidence interval [CI], 49.7% - 74.1%). One year after vaccination, effectiveness was 73.1% (95% CI, 60.3% - 81.8%). One to 2 years after vaccination, effectiveness dropped to 54.9% (95% CI, 32.4% - 70.0%). Two to 4 years after vaccination, Tdap effectiveness further decreased to 34.2% (95% CI, 20.03% - 58.0%).

The mixed-vaccine group (386 cases, 1076 controls) had an overall vaccine effectiveness of 51.5% (95% CI, 26.1% - 68.1%). Analyses suggested similar vaccine effectiveness for less than and more than 4 years after vaccination in this group (less than 48 months: 51.5% [95% CI, 24.3% - 69%]; 48 - 84 months: 52.2% [95% CI, 24.6% - 69.6%]).

These results suggest limited lasting protection against pertussis, regardless of type of vaccine received, the authors point out. Acellular vaccines, however, may have higher rates of waning protection.

Further analyses suggest slightly greater vaccine effectiveness with Boostrix (GlaxoSmithKline) compared with Adacel (Sanofi Pasteur; 56.5 [95% CI, 31.7 - 72.3] vs 39.2 [95% CI, 0.04 to 62.8]). Overlapping confidence intervals, however, preclude any definitive conclusions about the effectiveness of specific vaccines, the authors point out.

Dr Acosta and colleagues highlight the need for further research about the immunology of pertussis, as well as the need for more effective pertussis vaccines. They also emphasize the need to prioritize vaccination of infants, who are at the highest risk for serious illness and death from pertussis, and stress recent recommendations for Tdap during pregnancy.

"The duration of Tdap effectiveness is disappointing, particularly because case-control studies tend to inflate efficacy," writes James Cherry, MD, from the David Geffen School of Medicine at the University of California, Los Angeles, in an accompanying editorial.

Rapidly waning protection after natural infection could account for some of the resurgence in pertussis, according to Dr Cherry. He points out that the increase in reported rates of pertussis began about 14 years before the switch to Dtap. Differences in antibody response to the vaccines in children compared with adolescents and adults could also play a role.

"The 2 greatest contributors to the resurgence of pertussis are greater awareness and more sensitive diagnosis (the routine use of polymerase chain reaction)," Dr Cherry asserts.

Nevertheless, Dr Cherry agrees with Dr Acosta and colleagues about the importance of vaccination: "It is my opinion that we should continue with our present Tdap schedules," he concluded, "Of most importance is to see that all pregnant women receive Tdap with each pregnancy. This alone can prevent virtually all pertussis deaths in young infants."

The authors have disclosed no relevant financial relationships. Dr Cherry reports serving as a member of the speaker's bureau for Sanofi Pasteur, being a member of the Global Pertussis Initiative supported by Sanofi Pasteur, and receiving royalties from Elsevier for a textbook about pediatric infectious diseases.

Pediatrics. Published online May 4, 2015.

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