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.

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.

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

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.