Safety and Immunogenicity of Tetanus Diphtheria and Acellular Pertussis (Tdap) Immunization During Pregnancy in Mothers and Infants

Abstract

Importance Maternal immunization with tetanus toxoid and reduced diphtheria toxoid acellular pertussis (Tdap) vaccine could prevent infant pertussis. The effect of vaccine-induced maternal antibodies on infant responses to diphtheria and tetanus toxoids acellular pertussis (DTaP) immunization is unknown. Objective To evaluate the safety and immunogenicity of Tdap immunization during pregnancy and its effect on infant responses to DTaP. Design, Setting and Participants Phase I, randomized, double-masked, placebo-controlled clinical trial conducted in private (Houston) and academic (Durham, Seattle) obstetric practices from 2008 to 2012. Forty eight healthy 18–45 year-old pregnant women received Tdap (n=33) or placebo (n=15) at 30–32 weeks’ gestation with cross-over Tdap immunization postpartum. Interventions Tdap vaccination at 30–32 weeks’ gestation or post-partum. Outcome Measures Primary: Maternal and infant adverse events, pertussis illness and infant growth and development (Bayley-III screening test) until 13 months of age. Secondary: Antibody concentrations in pregnant women before and 4 weeks after Tdap immunization or placebo, at delivery and 2 months postpartum, and in infants at birth, 2 months, and after the third (7 months) and fourth (13 months) doses of DTaP. Results All participants delivered healthy newborns. No Tdap-associated serious adverse events occurred in women or infants. Injection site reactions after Tdap immunization were reported in 78.8% (95% CI: 61.1%, 91.0%) and 80% (CI: 51.9%, 95.7%) pregnant and postpartum women, respectively. Injection site pain was the predominant symptom. Systemic symptoms were reported in 36.4% (CI: 20.4%, 54.9%) and 73.3% (CI: 44.9%, 92.2%) pregnant and postpartum women, respectively. Malaise and myalgia were most common. Growth and development were similar in both infant groups. No cases of pertussis occurred. Significantly higher concentrations of pertussis antibodies were measured at delivery in women who received Tdap during pregnancy and in their infants at birth and at age 2 months when compared to infants of women immunized postpartum. Antibody responses in infants of Tdap recipients during pregnancy were modestly lower after 3 DTaP doses, but not different following the fourth dose. Conclusions and Relevance This preliminary safety assessment did not find an increased risk of adverse events among women who received Tdap vaccine at 30–32 weeks’ gestation or their infants. Maternal immunization with Tdap resulted in high concentrations of pertussis antibodies in infants during the first 2 months of life and did not substantially alter infant responses to DTaP. Further research is needed to provide definitive evidence of the safety and efficacy of Tdap vaccination during pregnancy. Trial Registration ClinicalTrials.gov, study identifier: NCT00707148. URL: http://www.clinicaltrials.gov

Factors influencing innate immunity and vaccine responses in infancy

“…B 370: 20140148 own response to vaccination. When comparing vaccine responses in infants born to mothers who had or had not received immunization against pertussis in pregnancy, the rises in antibody titres in infants born to vaccinated mothers have not been as substantial, but our own data and data from other groups indicate that the overall infant antibody responses to the routine childhood vaccines are well within the range of putative protection [30,31]. Administration of the influenza vaccine to pregnant women has also shown significant positive impact on both maternal and infant health: pregnant women who received H1N1 influenza vaccine were less likely to give birth preterm, and their babies were heavier at birth [32].…”

Vacunación con pertussis en el embarazo: una estrategia segura y efectiva para proteger al lactante menor

“…In addition, at the moment birth and at two months of age, the children of vaccinated women had significantly elevated antibody titers versus placebo. At 4 months of age, though, this difference was not evident 21 .…”

“…Several studies have demonstrated that immunization during pregnancy with acellular pertussis vaccine (Tdap) produces an elevation in IgG class antibody titres in pregnant women, and consequently an elevation in antibody titres in newborn plasma as well 1,[19][20][21] . This phenomenon is not observed when maternal immunization is performed prior to pregnancy 22 .…”

Experience and challenges on influenza and pertussis vaccination in pregnant women

“…An exception was for antibodies to FHA where infants from vaccinated mothers had approximately 2-times lower antibody concentration (p<0.01) at 7 months of age, after receipt of 3 doses of pertussis containing vaccine; this difference was however non-significant at 13 months of age, 1 month after the fourth dose of pertussis vaccine. 53 In another study from Vietnam, maternal vaccination with aP containing vaccine was associated with reduced immunogenicity to pertactin, but not against PT or FHA after the primary series of infant pertussis vaccination. 56 Nonetheless, 1 month after the booster dose antibody titers were similar for the 3 pertussis antigens tested in infants born to mothers who received aP containing vaccine and those born to mothers vaccinated with a tetanus-only vaccine.…”

“…concentration in infant equal or greater than in mother). 53 Moreover, immunization of pregnant women during early second trimester was associated with higher concentration of antibody in the newborn, possibly optimizing the effectiveness and durability thereof in the infant. 54 …”