Maternal Determinants of Infant Immunity to Pertussis

Phase 4

Recruiting

• Conditions: Vaccination; Infection; Immunoglobulins; Maternal-Fetal Relations; Pertussis
• Interventions: Biological: Triaxis® (Pertussis-containing vaccine); Biological: Vaxelis® (Pertussis-containing vaccine)

• Registration Number: NCT05856396
• Lead Sponsor: Centre Hospitalier Universitaire Saint Pierre

Brief Summary

The overall objective of the project is to identify the determinants of antibody-mediated immunity in infants born to mothers immunized during pregnancy. Using maternal pertussis immunization as a model, the project will identify key predictors and potential determinants of vaccine responses in pregnant women, of the transfer of maternal antibodies to the newborn and of vaccine responses in infants. A systems biology approach will be used to delineate pre-vaccination and post-vaccination cellular and molecular correlates of the immune response to pertussis immunization in peripheral blood and in breastmilk.

Detailed Description

The overall objective of the project is to identify the determinants of antibody-mediated immunity to pertussis in infants born to mothers immunized during pregnancy. Three specific objectives will be targeted:

1. Determine the impact of pregnancy on the quality of antibody response to pertussis immunization and identify immune predictors of vaccine responses in pregnant and non-pregnant women.

2. Identify immune predictors of the transfer of maternal antibodies to the newborn and the presence of antibody in breastmilk following pertussis immunization during pregnancy.

3. Determine the impact of maternal antibodies on the quality of antibody response to pertussis immunization in infants born to mothers immunized or not immunized during pregnancy and identify immune predictors of vaccine responses in the first months of life.

To reach these objectives, 40 non-pregnant and 80 pregnant women will be recruited into the study and vaccinated with a single dose of a pertussis containing vaccine (Triaxis). Blood samples will be collected from:

* non-pregnant women: before vaccination, and day 1/7/28 and month 5 post-vaccination.

* pregnant women: before vaccination, day 1/7/28 post-vaccination, at delivery, and week 6/12 post-delivery. At week 6/12 post-delivery, breast milk samples will be collected as well.

At delivery, a placenta fragment will be collected.

In addition, infants 2-3 months old born either from mothers who were not vaccinated against pertussis during pregnancy (n=40) or born from mothers who were vaccinated against pertussis during pregnancy (n=80) will be recruited in the study. Infants will be vaccinated with three doses of a pertussis containing vaccine (Vaxelis), each one month apart starting from 2-3 months of age. Blood samples will be collected from:

* infants from vaccinated mothers: cord blood, before 1st vaccine dose, day 1 post 1st vaccine dose, before 3rd vaccine dose, and day 28 post 3rd vaccine dose.

* infants from unvaccinated mothers: before 1st vaccine dose, day 1 post 1st vaccine dose, before 3rd vaccine dose, and day 28 post 3rd vaccine dose.

Study Timeline

• Study First Submitted: 2022-10-05
• Study First Submitted QC: 2023-05-03
• Study First Posted: 2023-05-12
• Study Start: 2023-09-12
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-17
• Last Update Posted: 2025-02-19
• Primary Completion: 2025-08
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• For non-pregnant & pregnant women Age between 18 and 45 years Eligible for Tdap vaccination
• For infants Born to mothers vaccinated or not with Tdap Vaccinated with hexavalent vaccine Age between 2 and 3 months

Exclusion Criteria

• For pregnant and non-pregnant women

  • Inability to understand the nature and extent of the study and the procedures required
  • Grade III/IV anemia,
  • Acute infection at the time of immunization
  • Chronic infections such as Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV) infection, acute toxoplasmosis
  • Current or recent use of immunosuppressive drugs
  • Active neoplasia
  • Other vaccine(s) administered at the same time as Tdap vaccination (wash out of 4 weeks after others vaccinations and 28 days after Tdap vaccination )

• For pregnant women

  • Risk of premature delivery or intrauterine growth retardation
  • Twin or triplet pregnancies

• For non-pregnant women Last Tdap vaccination < 12 months before

For infants:

• Infants born before 35 weeks of gestation
• Birthweight below 2.5 kg,
• Severe neonatal distress
• Serious congenital abnormalities or congenital infection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Non pregnant women	Triaxis® (Pertussis-containing vaccine)	Non-Pregnant women will receive one dose of Pertussis-containing vaccine.
Infants born to non Tdap-vaccinated mothers	Vaxelis® (Pertussis-containing vaccine)	Infants whose mothers have not been immunized during pregnancy with Tdap vaccine. Infants will receive three doses of Pertussis-containing vaccine (with 28 days interval starting at two months of age).
Pregnant women	Triaxis® (Pertussis-containing vaccine)	Pregnant women will receive one dose of Pertussis-containing vaccine during pregnancy.
Infants born to Tdap-vaccinated mothers	Vaxelis® (Pertussis-containing vaccine)	Infants whose mothers have been immunized during pregnancy with Tdap vaccine. Infants will receive three doses of Pertussis-containing vaccine (with 28 days interval starting at two months of age).

Primary Outcome Measures

Name	Time	Method
IgG titers specific to Bordetella Pertussis Antigens by Enzyme-linked immunosorbent assay (ELISA)	At delivery	IgG titers specific to Bordetella Pertussis Antigens will be assessed by ELISA: * in women vaccinated during pregnancy, at delivery; * in umbilical cord blood of infants born to mothers vaccinated during pregnancy

Secondary Outcome Measures

Name	Time	Method
IgG titers specific to Bordetella Pertussis Antigens by Enzyme-linked immunosorbent assay (ELISA)	up to 9 month after vaccination	IgG titers specific to Bordetella Pertussis Antigens will be assessed by ELISA: * in pregnant women (PW): at day of vaccination , day 7 post-vaccination, week 6 and 12 post-delivery; * in non-pregnant women (non PW): at day of vaccination, day 7 and Month 5 post-vaccination; * in infants (from unvaccinated mothers and mothers vaccinated during pregnancy) at day of first and third vaccine dose
CD4+ T cell frequencies specific to Bordetella Pertussis Antigens by flow cytometry	up to 9 month after vaccination	The percentage of CD4+ T cells expressing any of the following biomarkers (CD154, Interferon gamma, IL-2) in response to in vitro stimulation with Bordetella Pertussis Antigens will be measured by flow cytometry: i. in pregnant and non-pregnant women: at day of vaccination, and day 28 post vaccination; ii. in infants (from unvaccinated mothers and mothers vaccinated during pregnancy) at day of first vaccine dose and 28 days after third vaccine dose

Trial Locations

Locations (1)

CHU Saint-Pierre; 🇧🇪 Brussels, Belgium