Preterm Immune System Development and Response to Immunization

Study Overview
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Brief Summary
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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
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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.

Official Title
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Preterm Immune System Development and Response to Immunization

Conditions
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Immune System Disorder, Preterm, Vaccination Failure

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 2 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| preterm<br>preterm infants gestational age less than 32 weeks | |
| healthy controls<br>healthy term infants | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immune system development, preterm infant, vaccination