Clinical trial NCT02511327: Pertussis Immunization During Pregnancy: Effect in Term and Preterm Infants
Official title: Pertussis Immunization During Pregnancy: Assessment of the Role of Maternal Antibodies on Immune Responses in Term and Preterm Infants: the MAMA Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pertussis
Keywords: Pertussis
Pregnancy
Vaccination
Preterm
Breast milk
Humoral immune response
Cellular immune response
Maternal antibodies
Lead sponsor: Universiteit Antwerpen
Sponsor class: OTHER
Collaborators: name: University Hospital, Antwerp
name: Université Libre de Bruxelles
name: Research Foundation Flanders
First posted: 2015-07-30
Enrollment: 232
Sex: ALL
Minimum age (years): 0
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_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.

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.


Eligibility criteria: Inclusion Criteria for participating women:

* 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

Exclusion Criteria for participating women:

* 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

Exclusion Criteria for children:

* 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.

Primary outcomes:
measure: Titers of maternal pertussis specific antibodies
timeFrame: From birth until 8 weeks of age
Secondary outcomes:
measure: Titers of pertussis specific antibodies in infants after 3 doses of a pertussis vaccine
timeFrame: At the age of 5 months
measure: Titers of pertussis specific antibodies in infants before and after a fourth dose of a pertussis vaccine
timeFrame: From 13 to 16 months
measure: Titers of pertussis specific antibodies in infants in-between the fourth and fifth dose of a pertussis vaccine
timeFrame: Around 3 years of age
measure: Titers of pertussis specific antibodies in infants before and after a fifth dose of a pertussis vaccine
timeFrame: From 5 to 6 years of age
measure: Th1 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines
timeFrame: From 8 weeks of age until 16 months of age
measure: Th2 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines
timeFrame: From 8 weeks of age until 16 months of age
measure: Th1 & Th2 immune responses in preterm and term born infants before and after a fifth booster dose of a pertussis vaccine
timeFrame: From 5 to 6 years of age
measure: Titers of pertussis specific IgA antibodies in breast milk
timeFrame: From birth until 3 months postpartum
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University of Antwerp
Study officials:
affiliation: Universiteit Antwerpen
name: Elke Leuridan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.