Safety and Immunogenicity of Tdap Vaccine Immunization During Pregnancy

Immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy results in higher levels of antibodies early in infancy, but lower levels after completion of the primary vaccine series, according to a study published in Clinical Infectious Diseases.

There has been a recent resurgence of pertussis, an acute respiratory tract infection most severely affecting infants, despite widespread childhood vaccination. The first dose of pertussis vaccine may provide some protection against fatal infection, but full protection is not achieved until completion of the primary series, leaving infants susceptible for at least the first 2 to 3 months of life. Immunization during pregnancy to protect newborns through transplacental transfer of antibodies has been proposed and is recommended in some countries. Although maternal antibody protects the newborn infant, high levels of transplacentally acquired antibody might blunt the immune response to active immunization. Therefore, this randomized, controlled, multicenter study (ClinicalTrials.gov identifier: NCT00553228) examined the safety and immunogenicity of an adult formulation of Tdap or tetanus-diphtheria vaccine (Td) given in the third trimester of pregnancy and studied the effect of passive antibody on the postimmunization antibody response in the newborn.

A total of 273 healthy pregnant women age 18 to 45 who were assessed at ≥30 weeks’ gestation to be at low risk for complications were included and received either Tdap (n=135) or Td (n=138) vaccine in the third trimester. Women provided information for the safety analysis and samples for the immunogenicity analyses. A total of 261 infants provided serum for the immunogenicity analyses. Safety and immunogenicity of Tdap during pregnancy and the effect on the infant’s immune response to primary vaccination was measured at 2, 4, and 6 months and booster vaccination at 12 months of age.

Injection-site pain was reported by >80% of both Td and Tdap recipient. Mild fatigue (P =.041) and mild muscle aches (P =.014) were more common in Td than in Tdap recipients. Severe muscle aches were more common in Tdap recipients (P =.014). Serious adverse events were reported in both Td (n= 8) and Tdap (n=6) recipients, although none were determined to be vaccine related. There were 17 serious complications of pregnancy/labor (9 in Td recipients and 8 in Tdap recipients); 4 events were assessed as possibly vaccine related (preeclampsia, premature delivery, as well as hemolysis, elevated liver enzymes, low platelet count syndrome in 1 Td recipient, and gestational hypertension in 1 Tdap recipient).

Both Td and Tdap were immunogenic when given to pregnant women and steadily declined by 12 months postpartum. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and at 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM.

Overall, the investigators conclude that, “[their] study provides further support regarding the tolerability of Tdap when given during pregnancy” and also “provides new data concerning the blunting of the immune response to active, primary series immunization in infants of women immunized with Tdap during pregnancy.”

Reference

Halperin SA, Langley JM, Ye L, et al. A randomized controlled trial of the safety and immunogenicity of tetanus, diphtheria, and acellular pertussis vaccine immunization during pregnancy and subsequent infant immune response [published online July 13, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy244.