Clinical trial NCT05266664: Preterm Immune System Development and Response to Immunization
Official title: Preterm Immune System Development and Response to Immunization
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Immune System Disorder
Preterm
Vaccination Failure
Keywords: immune system development
preterm infant
vaccination
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Medical Center Haaglanden
name: Amphia Hospital
name: Albert Schweitzer Hospital
name: Franciscus Gasthuis
name: Maasstad Hospital
name: Maxima Medical Center
name: Reinier de Graaf Groep
name: Erasmus Medical Center
name: Merck Sharp & Dohme LLC
name: Zuyderland Medical Centre
name: Haga Hospital
First posted: 2022-03-04
Enrollment: 145
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For this study 120 preterm infants (GA\< 32 weeks) and their mothers will be enrolled to evaluate the antibody response to vaccination and the development of the immune system. In a subgroup of 25 preterm infants after maternal Tdap vaccination and 25 preterm infants whose mothers did not receive Tdap vaccination, Ag-specific memory B cell response to vaccination will be studied. For comparison of Ag-specific memory B cell development 25 healthy term infants and their mothers will also be recruited.

Brief summary: In this study the response to vaccination and development of the immune system in very preterm infants upon the current vaccination schedule will be compared to healthy term infants.

Detailed description: Preterm infants are at increased risk of developing infections early in life due to a less mature immune system compared to full-term infants. Moreover, protection by the placental transfer of maternal antibodies in general and specifically against vaccine antigens has shown to be significantly lower in very preterm infants (gestational age (GA)\< 32 weeks) compared to term infants. In this study we aim to investigate the immune system development of very preterm infants. Adequate immune response to vaccination is considered both clinically important as well as a functional test of the immune system. However, data on the antibody and Ag-specific memory B cell response to vaccination in preterm infants are limited.

Primary objective is to study the antibody immune response to routine vaccinations in very preterm infants (GA\<32 weeks). Secondary aim is to study the immune system more extensively using flow cytometry, ELISA and single cell transcriptomics to measure development of Ag-specific memory B cells raised in response to vaccination, and by using proteomics, epigenetics, and microbiome studies.

Eligibility criteria: To be eligible to participate in this study, a preterm infant must meet all following criteria:

* Preterm infant born at gestational age less than 32 weeks (whose mothers did or did not receive a T dap vaccination during pregnancy)
* Parents/ guardians must have sufficient understanding of the Dutch language

To be eligible to participate in this study, a healthy full-term infant must meet all following criteria:

* healthy full-term infant whose mother received a Tdap vaccination during pregnancy
* Parents/ guardians must have sufficient understanding of the Dutch language

To be eligible to participate in this study, a mother must meet all following criteria:

- Mother of preterm or health full-term infant who are participating in the study

Exclusion Criteria:

* Parents/guardians of the infant are not able or willing to provide informed consent
* Infant with congenital anomaly which are more likely to cause adverse effects after immunization (for example hemodynamically significant congenital heart defect)
* Infant with a (possible) HIV infection or immunodeficiency
* Maternal use of immunosuppressive drugs during pregnancy

Primary outcomes:
measure: antibody immune response to routine vaccinations in very preterm infants
timeFrame: 6 months
Secondary outcomes:
measure: IgG antibody concentrations following booster of routine vaccination with Vaxelis
timeFrame: 12 months
measure: geometrical mean concentrations following primary series and booster of routine vaccination with Vaxelis.
timeFrame: 6 and 12 months
measure: IgG antibody concentrations following routine vaccinations with 10-valent pneumococcal conjugate vaccine after primary series and booster vaccination.
timeFrame: 6 and 12 months
measure: IgG antibody concentrations against pertussis antigens at 2 months of age in preterm-born infants after maternal Tdap vaccination and in infants whose mother did not receive maternal Tdap vaccination.
timeFrame: 2 months
measure: number of antigen-specific memory B cells in cells/microliter following routine vaccinations after primary series and booster vaccination
timeFrame: 6 and 12 months
measure: IgG antibody concentrations in relation to maternal antibody concentrations against vaccine antigens
timeFrame: birth, 2,6 and 12 months
measure: comparison of response to vaccination between preterm infants and healthy term infants
timeFrame: 6 and 12 months
measure: Comparison of number of antigen-specific memory B cells in cells/microliter with and without preceding maternal Tdap vaccination
timeFrame: 6 and 12 months
Other outcomes:
Locations:
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Delft
country: Netherlands
facility: reinier de Graaff Group
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
city: Rotterdam
country: Netherlands
facility: Maasstad Hospital
city: Veldhoven
country: Netherlands
facility: Maxima Medical Center
Study officials:
affiliation: Maastricht UMC
name: Gertjan Driessen, Prof MD PhD
role: STUDY_DIRECTOR
affiliation: Medical Center Haaglanden
name: Jantien Bolt-Wieringa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Collins A, Weitkamp JH, Wynn JL. Why are preterm newborns at increased risk of infection? Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F391-F394. doi: 10.1136/archdischild-2017-313595. Epub 2018 Jan 30.
citation: Heininger U, Riffelmann M, Leineweber B, Wirsing von Koenig CH. Maternally derived antibodies against Bordetella pertussis antigens pertussis toxin and filamentous hemagglutinin in preterm and full term newborns. Pediatr Infect Dis J. 2009 May;28(5):443-5. doi: 10.1097/INF.0b013e318193ead7.
citation: van den Berg JP, Westerbeek EA, Berbers GA, van Gageldonk PG, van der Klis FR, van Elburg RM. Transplacental transport of IgG antibodies specific for pertussis, diphtheria, tetanus, haemophilus influenzae type b, and Neisseria meningitidis serogroup C is lower in preterm compared with term infants. Pediatr Infect Dis J. 2010 Sep;29(9):801-5. doi: 10.1097/inf.0b013e3181dc4f77.
citation: Wilck MB, Xu ZJ, Stek JE, Lee AW. Safety and immunogenicity of a fully-liquid DTaP-IPV-Hib-HepB vaccine (Vaxelis) in premature infants. Hum Vaccin Immunother. 2021 Jan 2;17(1):191-196. doi: 10.1080/21645515.2020.1756668. Epub 2020 Aug 4.
citation: Barug D, Pronk I, van Houten MA, Versteegh FGA, Knol MJ, van de Kassteele J, Berbers GAM, Sanders EAM, Rots NY. Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial. Lancet Infect Dis. 2019 Apr;19(4):392-401. doi: 10.1016/S1473-3099(18)30717-5. Epub 2019 Mar 27.
citation: Syed YY. DTaP5-HB-IPV-Hib Vaccine (Vaxelis(R)): A Review of its Use in Primary and Booster Vaccination. Paediatr Drugs. 2017 Feb;19(1):69-80. doi: 10.1007/s40272-016-0208-y.
citation: Vono M, Eberhardt CS, Auderset F, Mastelic-Gavillet B, Lemeille S, Christensen D, Andersen P, Lambert PH, Siegrist CA. Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers. Cell Rep. 2019 Aug 13;28(7):1773-1784.e5. doi: 10.1016/j.celrep.2019.07.047.