Preterm Immune System Development and Response to Immunization

Preterm Clinical Trial

— PRIMI  

Official title:

Preterm Immune System Development and Response to Immunization

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05266664
• Other study ID #: NL80118.068.22
• Status: Recruiting
• Start date: December 8, 2022
• Est. completion date: July 2026

Study information

• Verified date: March 2024
• Source: Maastricht University Medical Center
• Contact: Gertjan Driessen, Prof MD PhD
• Phone: +31433876543
• Email: gertjan.driessen[@]mumc.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 145
• Est. completion date: July 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 2 Months

Eligibility

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

Related Conditions & MeSH terms

• Immune System Diseases
• Immune System Disorder
• Premature Birth
• Preterm
• Vaccination Failure

Locations

Country	Name	City	State
Netherlands	Amphia Hospital	Breda
Netherlands	reinier de Graaff Group	Delft
Netherlands	Albert Schweitzer Hospital	Dordrecht
Netherlands	Erasmus MC	Rotterdam
Netherlands	Franciscus Gasthuis	Rotterdam
Netherlands	Maasstad Hospital	Rotterdam
Netherlands	Maxima Medical Center	Veldhoven

Sponsors (12)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Albert Schweitzer Hospital, Amphia Hospital, Erasmus Medical Center, Franciscus Gasthuis, Haga Hospital, Maasstad Hospital, Maxima Medical Center, Medical Center Haaglanden, Merck Sharp & Dohme LLC, Reinier de Graaf Groep, Zuyderland Medical Centre

Country where clinical trial is conducted

Netherlands, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	antibody immune response to routine vaccinations in very preterm infants	IgG antibody concentrations against six vaccine antigens in preterm-born infants following primary series of routine vaccinations with Vaxelis in order to assess the proportion of children with IgG concentrations above international-defined thresholds for protection.	6 months
Secondary	IgG antibody concentrations following booster of routine vaccination with Vaxelis	IgG antibody concentrations against vaccine antigens in preterm-born infants following booster of routine vaccination with Vaxelis.	12 months
Secondary	geometrical mean concentrations following primary series and booster of routine vaccination with Vaxelis.	geometrical mean concentrations in preterm infants compared to reference values in healthy term infants as known from literature following primary series and booster of routine vaccination with Vaxelis.	6 and 12 months
Secondary	IgG antibody concentrations following routine vaccinations with 10-valent pneumococcal conjugate vaccine after primary series and booster vaccination.	IgG antibody concentrations against vaccine antigens in preterm-born infants following routine vaccinations with 10-valent pneumococcal conjugate vaccine after primary series and booster vaccination.	6 and 12 months
Secondary	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.	IgG antibody concentrations against pertussis antigens at 2 months of age (before start of infant immunizations) in preterm-born infants after maternal Tdap vaccination and in infants whose mother did not receive maternal Tdap vaccination.	2 months
Secondary	number of antigen-specific memory B cells in cells/microliter following routine vaccinations after primary series and booster vaccination	number of antigen-specific memory B cells in cells/microliter in preterm-born infants following routine vaccinations after primary series and booster vaccination	6 and 12 months
Secondary	IgG antibody concentrations in relation to maternal antibody concentrations against vaccine antigens	IgG antibody concentrations against vaccine antigens in preterm-born infants before start of immunizations and following routine vaccinations after primary series and booster vaccination, in relation to maternal antibody concentrations against vaccine antigens	birth, 2,6 and 12 months
Secondary	comparison of response to vaccination between preterm infants and healthy term infants	Proportions of infants with IgG concentrations above the internationally defined threshold for protection and geometrical mean concentrations will be compared between preterm infants after maternal Tdap vaccination, preterm infants whose mothers did not receive Tdap vaccination and reference values in healthy term infants as known from literature.	6 and 12 months
Secondary	Comparison of number of antigen-specific memory B cells in cells/microliter with and without preceding maternal Tdap vaccination	Number of antigen-specific memory B cells in cells/microliter will be compared between preterm infants after maternal Tdap vaccination, preterm infants whose mothers did not receive Tdap vaccination and healthy term infants after maternal Tdap vaccination, who will be recruited for this study.	6 and 12 months