Newborns, especially those born preterm, are at high risk for infection. Preterm birth rates appear to be increasing in most countries, with ∼15 million infants born preterm globally each year, corresponding to ∼11% of all deliveries. Importantly, the vulnerability of preterm infants to infection continues beyond the perinatal period, following them throughout childhood and adolescence, highlighting the long-lasting effects of infection on overall health and well-being. Other than access to clean drinking water and proper sewage systems, immunization is the most effective biomedical intervention to reduce early life infection. Nevertheless, a significant proportion of infants discharged on or after 2 months of age from the NICU remains unimmunized or underimmunized at that time. Despite being safe and effective, protective responses to immunization in early life are different from those in older individuals, in part because of the distinct immune system of newborns and young infants. The paradigms of the Bacille Calmette-Guérin, hepatitis B, and polio vaccines, the only immunizations currently routinely administered in the neonatal period, provide evidence that it is feasible to successfully administer vaccines via different routes of delivery; thus, production of sufficient vaccine-induced immunity leads to disease prevention in the newborn. Strategies such as maternal immunization, adjuvantation systems, leveraging trained immunity, and counseling caregivers can be used to enhance vaccine-induced specific and heterologous protection from infection and boost adherence to the recommended immunization schedule.

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