The purpose of this study is to look at the safety and immunogenicity of a combination vaccine that includes tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). The study will be conducted in 48 pregnant women and 32 non-pregnant women. Safety of the newborn infant and the effect of the mother's vaccination on the infants' immune responses prior to vaccinating infants with another combination vaccine to protect against diphtheria, tetanus, and pertussis will be evaluated. Participants will be 18-45 years old. Pregnant volunteers will be 30-32 weeks pregnant and at a low risk for pregnancy complications. Pregnant volunteers will receive 2 injections (1 vaccine and 1 placebo, inactive substance); non-pregnant volunteers will receive 1 injection of vaccine. Blood samples will be collected from the mother and infant, along with the baby's growth measurements. Participation for mother infant pairs is about 15 months and about 7 months for non-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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
80
Saline (0.9% NaCl) administered as a single 0.5 mL intramuscular injection into the deltoid.
Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine absorbed (Tdap). Administered as a single 0.5 mL intramuscular injection into the deltoid.
Duke University Medical Center - Duke Perinatal Clinic
Durham, North Carolina, United States
Baylor College of Medicine - Molecular Virology and Microbiology
Houston, Texas, United States
Group Health Research Institute - Seattle
Seattle, Washington, United States
Seattle Children's Hospital - Infectious Diseases
Seattle, Washington, United States
Incidence of injection site and systemic reactions following injections.
Time frame: Recorded 0 to 7 days after injection.
Frequency of vaccine-associated adverse events (AEs).
Time frame: 30 minutes post-injection, Day 0, 1-2, 7, 4 weeks post-injection, delivery, Day 1-2, 7, and 2 and 4 months post-delivery. Infant AEs: Delivery, 2, 4, 7, and 13 months. Non-pregnant: Day 0, 1-2, 7, 4 weeks and 6 months.
Frequency of vaccine-associated serious adverse events (SAEs).
Time frame: Maternal SAEs through 4 months post delivery and infant SAEs from delivery to 13 months. Non-pregnant SAEs: Day 0 through to 6 months post-injection.
Infant growth measurements (fronto-occipital circumference [FOC], length and weight).
Time frame: At delivery and at 2, 7 and 13 months of age.
Bayley III developmental screening of infants.
Time frame: At age 13 months.
Incidence of pertussis infection captured by surveillance for adverse events (AEs) and serious adverse events (SAEs).
Time frame: Duration of study, captured by surveillance for AEs and SAEs. Antepartum: Day 1-2 and 7; 4 weeks; delivery. Postpartum: Day 1-2 and 7; Month 2, 4,7, and 13.
Concentrations of immunoglobulin G (IgG) for pertussis toxin (PT), pertactin (PRN), fimbrial proteins (FIM), filamentous hemagglutinin (FHA), tetanus toxoid (TT), and diphtheria toxoid (DT).
Time frame: Mother: blood samples collected before and 4 weeks after antepartum injection, at hospital admission for delivery and at the 2 month post delivery visit. Infant: collected at delivery (cord), 2, 7 and 13 months of age.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.