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| Name | Class |
|---|---|
| University Hospital, Antwerp | OTHER |
| Université Libre de Bruxelles | OTHER |
| Research Foundation Flanders | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
| |
| 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. |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infant pertussis vaccination | Drug | Infants receive pertussis vaccines according to the national recommended schedule |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Titers of pertussis specific antibodies in infants after 3 doses of a pertussis vaccine | Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken at 5 months (after a primary series of 3 vaccines) | At the age of 5 months |
| Titers of pertussis specific antibodies in infants before and after a fourth dose of a pertussis vaccine |
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Inclusion Criteria for participating women:
Exclusion Criteria for participating women:
Exclusion Criteria for children:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Elke Leuridan, MD, PhD | Universiteit Antwerpen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Antwerp | Antwerp | 2000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37285482 | Derived | 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. | |
| 36528443 | Derived | 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. |
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| ID | Term |
|---|---|
| D014917 | Whooping Cough |
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D001885 | Bordetella Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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Blood samples and breast milk samples
|
Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth 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 | Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth pertussis vaccine | Around 3 years of age |
| Titers of pertussis specific antibodies in infants before and after a fifth dose of a pertussis vaccine | Anti-Pertussis Toxin, anti-Filamentous Haemagglutinin and anti-pertactin immunoglobulin IgG titers, measured in blood samples taken before and 1 month after a fourth 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 | Measurement of Th1 markers in a convenience sample of infants after primary and booster pertussis vaccination | From 8 weeks of age until 16 months of age |
| Th2 immune responses in preterm and term born infants before and after a primary series of infant pertussis vaccines | Measurement of Th2 markers in a convenience sample of infants after primary and booster pertussis vaccination | From 8 weeks of age until 16 months of age |
| Th1 & Th2 immune responses in preterm and term born infants before and after a fifth booster dose of a pertussis vaccine | Measurement of Th1 and Th2 markers in a convenience sample of infants before and after a pertussis booster vaccination | From 5 to 6 years of age |
| Titers of pertussis specific IgA antibodies in breast milk | Measurement of anti-Pertussis Toxin IgA, total IgA and lactoferrin titers in breast milk samples taken at birth, at week 4, 8 and 12 | From birth until 3 months postpartum |
| 34849638 | Derived | 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. |
| 33971009 | Derived | 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. |
| 33768227 | Derived | 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. |
| D007239 | Infections |
| D012141 | Respiratory Tract Infections |
| D012140 | Respiratory Tract Diseases |
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |