NCT02511327

Brief Summary

Young infants are most vulnerable to severe disease and even death when infected with Bordetella Pertussis. The current vaccines and vaccination programs do not guarantee protection of neonates. During the last weeks of pregnancy, maternal IgG antibodies are transferred actively to the fetus. Administration of a pertussis containing vaccine during pregnancy offers protection through high titers of maternal antibodies transferred to the child. Since transplacental transport is immature, infants who are born prior to 37 weeks of gestation, might be vulnerable to pertussis infection even though maternal vaccination was administered, but specific data are lacking. The primary aim of this observational study is to measure whether vaccination during pregnancy offers protection to preterm born infants through higher titers of maternal antibodies, despite immature transplacental transport. Four cohorts of mother-infant pairs will be recruited: term versus preterm born infants, born from either vaccinated women or not vaccinated women. These mother-infant pairs are recruited according to the vaccination status of the mother and to the gestational age at delivery. Pertussis specific antibody titers (anti-Pertussis Toxin, anti-Filamentous haemagglutinin, anti-Pertactin titers) will be monitored in blood samples of the mothers at delivery to measure the possible influence of both gestational age and maternal vaccination status. In order to measure the decline of maternal antibodies in the first weeks of life, blood will be taken from cords as well as from infants at 8 weeks of age, before the first infant pertussis vaccine is administered. Pertussis antibodies to the same antigens will be measured in all infants after a primary series of acellular pertussis vaccines administered at 8,12 and 16 weeks of age and before and after a booster dose in the second year of life. In addition, cellular mediated immune responses will be evaluated in a subgroup of infants before and after a primary series of infants vaccines. A last goal is to measure whether vaccination during pregnancy could offer additional maternal antibodies through breast milk. Again a comparison is made between preterm and term born infants, born from either vaccinated or unvaccinated women. The amount of lactoferrin and pertussis toxin specific IgA in breast milk samples will be measured in samples taken at birth (colostrum), and at several time points afterwards as long as breastfeeding is continued.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
232

participants targeted

Target at P75+ for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2015

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

July 22, 2015

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 30, 2015

Completed
3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
Last Updated

January 15, 2021

Status Verified

January 1, 2021

Enrollment Period

4 years

First QC Date

July 22, 2015

Last Update Submit

January 12, 2021

Conditions

Pertussis

Keywords

PertussisPregnancyVaccinationPretermBreast milkHumoral immune responseCellular immune responseMaternal antibodies

Outcome Measures

Primary Outcomes (1)

  • Titers of maternal pertussis specific antibodies

    Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken from cord and at week 8 postpartum in all participating infants

    From birth until 8 weeks of age

Secondary Outcomes (8)

  • Titers of pertussis specific antibodies in infants after 3 doses of a pertussis vaccine

    At the age of 5 months

  • Titers of pertussis specific antibodies in infants before and after a fourth dose of a pertussis vaccine

    From 13 to 16 months

  • Titers of pertussis specific antibodies in infants in-between the fourth and fifth dose of a pertussis vaccine

    Around 3 years of age

  • Titers of pertussis specific antibodies in infants before and after a fifth dose of a pertussis vaccine

    From 5 to 6 years of age

  • Th1 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines

    From 8 weeks of age until 16 months of age

  • +3 more secondary outcomes

Study Arms (4)

Preterm born infants of vaccinated women

Preterm born infants (\< 37 weeks of gestation) whose mothers have received an acellular pertussis vaccine during pregnancy, within the national recommended vaccination programme. Infant vaccination against pertussis is performed according to the national recommended schedule.

Drug: Infant pertussis vaccination

Term born infants vaccinated women

Term born infants (\>= 37 weeks of gestation) whose mothers have received an acellular pertussis vaccine during pregnancy, within the national recommended vaccination programme. Infant vaccination against pertussis is performed according to the national recommended schedule.

Drug: Infant pertussis vaccination

Term born infants unvaccinated women

Term born infants (\>= 37 weeks of gestation) whose mothers have not received an acellular pertussis vaccine during pregnancy. Infant vaccination against pertussis is performed according to the national recommended schedule.

Drug: Infant pertussis vaccination

Preterm born infants unvaccinated women

Preterm born infants (\< 37 weeks of gestation) whose mothers have not received an acellular pertussis vaccine during pregnancy.Infant vaccination against pertussis is performed according to the national recommended schedule.

Drug: Infant pertussis vaccination

Interventions

Infant pertussis vaccinationDRUG

Infants receive pertussis vaccines according to the national recommended schedule

Also known as: Infant pertussis containing vaccination
Preterm born infants of vaccinated womenPreterm born infants unvaccinated womenTerm born infants unvaccinated womenTerm born infants vaccinated women

Eligibility Criteria

Age0 Years - 40 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodProbability Sample
Study Population

Four cohorts of women-infant pairs will be recruited before or directly after delivery. A cohort of preterm born infants will be compared to term born infants, and both will be compared within groups of vaccinated women (adult acellular pertussis containing vaccine) or unvaccinated women.

You may qualify if:

  • Pregnancy
  • Signed informed consent
  • Intend to be available for follow-up visits and phone call access through 16 months following delivery
  • Willing to have infant immunized with hexavalent vaccine according to the recommended Belgian schedule

You may not qualify if:

  • Significant mental illness (e.g. schizophrenia, psychosis, major depression)
  • Serious underlying immunological condition (e.g. immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection)
  • Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk
  • Receipt of a blood product or experimental medicine within 4 weeks prior to delivery
  • Multiple pregnancies
  • No signed informed consent from both parents
  • Severe reactions to any vaccine
  • Serious underlying medical condition (e.g., genetic disorder (eg Down syndrome), immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection, lung/heart disease, liver/kidney disease, chronic or recurrent infections)
  • Children suffering from primary humoral immune disorders (B cell related): severe X linked agammaglobulinaemia, CVID (Common variable immunodeficiency, late onset agammaglobulnaemia) and SAD (specific antibody deficiency); suffering from primary cellular immune deficiencies (T cell related): SCID (Severe combined immune deficiency syndrome), CID, hyper IGM syndrome, di George's syndrome and others; suffering from disorders in phagocytosis and chemotaxis (CGD, Schwach Diamond syndrome) and disorders from the complement cascade
  • In addition children with oncologic disorders will be excluded. All these children can receive the inactivated pertussis vaccines, but will respond different from the normal population to vaccination.
  • Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Antwerp

Antwerp, 2000, Belgium

Location

Related Publications (5)

  • Embacher S, Maertens K, Herzog SA. Half-life Estimation of Pertussis-Specific Maternal Antibodies in (Pre)Term Infants After In-Pregnancy Tetanus, Diphtheria, Acellular Pertussis Vaccination. J Infect Dis. 2023 Nov 28;228(11):1640-1648. doi: 10.1093/infdis/jiad212.

    PMID: 37285482DERIVED

  • Maertens K, Orije MRP, Huoi C, Boisnard F, Lyabis O. Immunogenicity of a liquid hexavalent DTaP-IPV-HB-PRP approximately T vaccine after primary and booster vaccination of term and preterm infants born to women vaccinated with Tdap during pregnancy. Vaccine. 2023 Jan 16;41(3):795-804. doi: 10.1016/j.vaccine.2022.12.021. Epub 2022 Dec 15.

    PMID: 36528443DERIVED

  • Orije MRP, Garcia-Fogeda I, Van Dyck W, Corbiere V, Mascart F, Mahieu L, Hens N, Van Damme P, Cools N, Ogunjimi B, Maertens K, Leuridan E. Impact of Maternal Pertussis Antibodies on the Infants' Cellular Immune Responses. Clin Infect Dis. 2022 Aug 31;75(3):442-452. doi: 10.1093/cid/ciab972.

    PMID: 34849638DERIVED

  • Maertens K, Orije MRP, Herzog SA, Mahieu LM, Hens N, Van Damme P, Leuridan E. Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm-Born Infants. Clin Infect Dis. 2022 Jan 29;74(2):189-198. doi: 10.1093/cid/ciab424.

    PMID: 33971009DERIVED

  • Orije MRP, Lariviere Y, Herzog SA, Mahieu LM, Van Damme P, Leuridan E, Maertens K. Breast Milk Antibody Levels in Tdap-Vaccinated Women After Preterm Delivery. Clin Infect Dis. 2021 Sep 15;73(6):e1305-e1313. doi: 10.1093/cid/ciab260.

    PMID: 33768227DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples and breast milk samples

MeSH Terms

Conditions

Whooping CoughPremature Birth

Condition Hierarchy (Ancestors)

Bordetella InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfectionsRespiratory Tract InfectionsRespiratory Tract DiseasesObstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Study Officials

  • Elke Leuridan, MD, PhD

    Universiteit Antwerpen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Elke Leuridan, MD, PhD

Study Record Dates

First Submitted

July 22, 2015

First Posted

July 30, 2015

Study Start

January 1, 2015

Primary Completion

January 1, 2019

Last Updated

January 15, 2021

Record last verified: 2021-01

Locations

BE(1)