Pertussis Vaccine in Healthy Pregnant Women

Pertussis, "whooping cough", caused by the gram negative pleomorphic bacillus, Bordetella pertussis, is a highly contagious, potentially life-threatening respiratory illness that has re-emerged in the United States (US) as a cause of morbidity and mortality in infants less than 6 months of age as well as morbidity in adolescents and adults. Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed (Tdap) immunization of women in the third trimester of pregnancy represents an opportunity to protect the vulnerable very young infants through passively acquired maternal pertussis specific antibodies. Tdap vaccine is being evaluated for this purpose since there is no monovalent acellular pertussis (aP) vaccine available in the U.S. This is a multi-site, randomized, double masked, cross-over study in 48 healthy pregnant women, 18-45 years of age who will be randomized (2:1) into two groups. One group will receive a single dose of Tdap vaccine at 30-32 weeks of gestation and a postpartum dose of saline. The other group will receive saline at 30-32 weeks of gestation and a postpartum dose of Tdap vaccine. On May 30, 2008 the Advisory Committee on Immunization Practices (ACIP) issued a recommendation for use of Tdap in pregnant and postpartum women: "Pregnant women (including women who are breastfeeding) who have not received a dose of Tdap previously should receive Tdap after delivery and before discharge from the hospital or birthing center if 2 years or more have elapsed since the most recent administration of Td." This study design provides a control for the evaluation of the safety of Tdap vaccine administered during pregnancy and provides compliance with the ACIP recommendation. Immune responses to Tdap vaccine measured in antepartum and postpartum women enrolled in this clinical trial will be compared. Also, immune responses of the 32 pregnant women antenatally immunized with Tdap will be compared to those in approximately 32 healthy non-pregnant women contemporaneously enrolled into 2 age groups (18-39 years and 40-45 years) that are equal to the pregnant women. The purpose of this study is to evaluate the safety of Tdap vaccine in pregnant women and their neonates and the effect of maternal immunization on the infant immune response to DTaP vaccinations. The safety of and immune response to Tdap vaccine in the 32 pregnant women immunized antenatally will be compared to that in approximately 32 non-pregnant women enrolled contemporaneously. The primary objectives of this phase I study are: to evaluate the safety of a single 0.5 mL intramuscular injection of Tdap vaccine in healthy pregnant women vaccinated at 30-32 weeks of gestation compared to women immunized postpartum and a non-pregnant control group; and to evaluate the safety of maternal Tdap immunization in neonates. Secondary objectives are: to assess the immunogenicity of Tdap vaccine in healthy pregnant women compared to women immunized postpartum and a non-pregnant control group; to determine the efficiency of placental transport of maternal pertussis specific antibodies to the neonate; to assess the persistence of the maternal pertussis specific antibodies in infants just prior to receiving the first dose of DTaP \[Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate\] vaccine for infants); and to assess the effects of maternal immunization with Tdap vaccine on infant immune responses to DTaP vaccinations. Study duration will be approximately 3 years. Subject participation will be approximately 15 months (for each mother-infant pair) and 7 months for non-pregnan