Pertussis remains a major global public health problem. In Thailand, pertussis vaccination is recommended during pregnancy at 20-32 weeks' gestation, together with routine childhood diphtheria-tetanus-pertussis vaccination administered as a primary series at 2, 4, and 6 months and booster doses at 18 months and 4-6 years of age. TdaP2gen, a newly developed combined tetanus, diphtheria, and recombinant genetically detoxified acellular pertussis vaccine containing 2 µg pertussis antigen, has shown favorable safety and non-inferior immunogenicity compared with existing pertussis vaccines. However, data on its use in pregnant women, transplacental antibody transfer, and potential immune interference in infants remain limited. This study aims to evaluate the safety and immunogenicity of TdaP2gen in pregnant women, assess antibody transfer to newborns, and investigate immune responses to tetanus, diphtheria, and pertussis following primary and booster pertussis-containing vaccinations in infants and toddlers, including comparisons between whole-cell and acellular pertussis-containing vaccine schedules.
Pertussis remains a major global public health problem. In Thailand, pertussis vaccination is recommended for all pregnant women at 20-32 weeks' gestation to protect newborns and young infants against pertussis during early life. In addition, combined diphtheria-tetanus-pertussis vaccination is routinely administered as a primary series at 2, 4, and 6 months of age, followed by booster doses at 18 months and 4-6 years of age. TdaP2gen is a combined tetanus, diphtheria, and recombinant genetically detoxified acellular pertussis vaccine, containing 2 µg pertussis antigen, which has been recently developed. Previous clinical studies have demonstrated that TdaP2gen is safe and elicits non-inferior immune responses against pertussis compared with the 5 µg recombinant acellular pertussis vaccine (TdaP5gen) and the chemically inactivated Tdap vaccine. However, as TdaP2gen is a newly licensed vaccine in Thailand, data on its safety, immunogenicity in pregnant women, placental antibody transfer to infants, and potential immune interference with infant responses to routine pertussis-containing vaccines remain limited. Therefore, this study aims to evaluate the safety and immunogenicity of TdaP2gen in pregnant women, assess transplacental antibody transfer to newborns, and investigate its impact on immune responses to diphtheria, tetanus, and pertussis following primary series and booster vaccination up to 15-18 months of age in infants and young children. This study is divided into 3 phases as follows: Phase 1 - Maternal and fetal phase: This phase will evaluate the immunogenicity and safety of TdaP2gen vaccination in pregnant women, including immune responses against tetanus, diphtheria, and pertussis, as well as the transplacental transfer of antibodies to newborns. Phase 2 - Infant phase: This phase will assess immune responses to tetanus, diphtheria, and pertussis in infants following completion of the primary pertussis-containing vaccine series at 2, 4, and 6 months of age, comparing infants who receive whole-cell pertussis-containing vaccines (wP-containing vaccines) with those who receive acellular pertussis-containing vaccines (aP-containing vaccines). Phase 3 - Toddler phase: This phase will evaluate immune responses to tetanus, diphtheria, and pertussis in toddlers after receiving a pertussis-containing booster vaccination at 15-18 months of age, comparing children who receive whole-cell pertussis-containing vaccines (wP-containing vaccines) with those who receive acellular pertussis-containing vaccines (aP-containing vaccines).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
320
A combined tetanus toxoid, reduced diphtheria toxoid, reduced-dose (2 µg) genetically-detoxified recombinant acellular pertussis vaccine (TdaP2gen)
An infant acellular pertussis (aP)-containing vaccine
An infant whole-cell pertussis (wP)-containing vaccine
Department of Pediatrics, Faculty of Medicine, Chiang Mai University
Chiang Mai, Thailand
Phase 1: Maternal anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid, and anti-tetanus toxoid immunoglobulin G (IgG) geometric mean concentrations and seroresponse rates following TdaP2gen vaccination during pregnancy
Assessment of maternal anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates before TdaP2gen vaccination, after vaccination, and at delivery
Time frame: Pre-vaccination baseline, 4 weeks after vaccination (+/- 14 days), and at delivery
Phase 1: Cord blood anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates at birth
Assessment of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates in cord blood collected at delivery among infants born to TdaP2gen vaccinated mothers
Time frame: At delivery
Phase 1: Incidence of solicited local and systemic adverse events, serious adverse events, and adverse pregnancy outcomes of TdaP2gen vaccination during pregnancy
Assessment of solicited local and systemic adverse events as well as serious adverse events and adverse pregnancy outcomes among pregnant women receiving TdaP2gen vaccination during pregnancy.
Time frame: From vaccination until delivery, assessed up to approximately 22 weeks post-vaccination.
Phase 2: Infant anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates following primary diphtheria-tetanus-pertussis vaccination series
Assessment and comparison of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates between infants born to mothers receiving TdaP2gen vaccine during pregnancy who are randomized to receive either aP- or wP-containing vaccines as the primary vaccination series during infancy
Time frame: Pre-primary series vaccination (within 2 months after birth) and post-primary series vaccination (at age 7 months +/- 14 days)
Phase 3: Infant anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates following booster diphtheria-tetanus-pertussis vaccination
Assessment and comparison of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates between infants born to mothers receiving TdaP2gen vaccine during pregnancy who previously received either aP or wP-containing vaccines during the primary vaccination series and subsequently receive booster vaccination at 15-18 months of age
Time frame: At 12 months of age (+/- 14 days), pre-booster vaccination, and 1 month after booster vaccination (+/- 14 days)
Phase 1: Maternal pertussis-neutralizing antibody geometric mean titers following TdaP2gen vaccination during pregnancy
Assessment of maternal pertussis-neutralizing antibody geometric mean titers in a subset of 40 pregnant women before TdaP2gen vaccination, after vaccination, and at delivery
Time frame: Pre-vaccination baseline, 4 weeks after vaccination (+/- 14 days), and at delivery
Phase 1: Cord blood pertussis-neutralizing antibody geometric mean titers at birth
Assessment of pertussis-neutralizing antibody geometric mean titers in cord blood samples from newborns of a subset of 40 vaccinated pregnant women at delivery
Time frame: At delivery
Phase 1: Knowledge and acceptability of pertussis and pertussis vaccine among pregnant women assessed using a structured questionnaire
Assessment of knowledge and acceptability of pertussis and pertussis vaccine among pregnant women using a structured questionnaire
Time frame: Pre-vaccination baseline
Phase 2: Infant pertussis-neutralizing antibody geometric mean titers following primary diphtheria-tetanus-pertussis vaccination series
Assessment and comparison of pertussis-neutralizing antibody geometric mean titers in a subset of 40 infants born to mothers receiving TdaP2gen vaccine during pregnancy who are randomized to receive either aP- or wP-containing vaccines as the primary vaccination series during infancy
Time frame: Pre-primary series vaccination (within 2 months after birth) and post-primary series vaccination (at age 7 months +/- 14 days)
Phase 2: Incidence of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following the primary diphtheria-tetanus-pertussis vaccination series in infants
Assessment and comparison of the frequency and severity of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following administration of aP- or wP-containing vaccines during the primary vaccination series in infants born to mothers receiving TdaP2gen vaccine during pregnancy
Time frame: From the first dose of the primary diphtheria-tetanus-pertussis vaccination series until 1 month after completion of the primary vaccination series, assessed up to approximately 5 months
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Phase 3: Infant pertussis-neutralizing antibody geometric mean titers following booster diphtheria-tetanus-pertussis vaccination
Assessment and comparison of pertussis-neutralizing antibody geometric mean titers in a subset of 40 infants born to mothers receiving TdaP2gen vaccine during pregnancy who previously received either aP or wP-containing vaccines during the primary vaccination series and subsequently receive booster vaccination at 15-18 months of age
Time frame: At 12 months of age (+/- 14 days), pre-booster vaccination, and 1 month after booster vaccination (+/- 14 days)
Phase 3: Incidence of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following booster diphtheria-tetanus-pertussis vaccination in infants
Assessment and comparison of the frequency and severity of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following administration of aP or wP booster vaccination in infants born to mothers receiving TdaP2gen vaccine during pregnancy
Time frame: From booster vaccination through 28 days after vaccination