Immunization of preterm infants: current evidence and future strategies to individualized approaches

Abstract

Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.

Persistence of antibodies 5 years after hepatitis B vaccination in preterm birth children: A retrospective cohort study using real‐world data

“…Thus, gestational and chronological age might be important factors in reducing immunogenicity to HepB, and preterm infants may require an additional dose or early booster vaccination. [26][27][28][29] Previous studies have shown that lower birth weight and smaller gestational age are associated with a decreased immune response after HepB vaccination, 27,30 implying that these factors may also affect the long-term persistence of HepB. Similar results were also observed in the current study.…”

“…1.1-2.0), and the overall GMC was significantly lower in the PTB exposure group compared to the control group (9.3 vs. 12.4 mIU/ mL). Moreover, Fortmann et al 28 considered that cell-mediated recall responses of preterm infant leukocytes to short HBV exposure were reduced as compared to term infants and dependent on pre-existing antibody levels. Thus, gestational and chronological age might be important factors in reducing immunogenicity to HepB, and preterm infants may require an additional dose or early booster vaccination.…”

“…We found that the risk of being HBsAb‐negative 5 years after HepB vaccination in the PTB exposure group was 1.5 times higher than that in the control group (aOR = 1.5, 95% CI: 1.1–2.0), and the overall GMC was significantly lower in the PTB exposure group compared to the control group (9.3 vs. 12.4 mIU/mL). Moreover, Fortmann et al 28 . considered that cell‐mediated recall responses of preterm infant leukocytes to short HBV exposure were reduced as compared to term infants and dependent on pre‐existing antibody levels.…”

Heterogeneity of tissue-resident immunity across organs and in health and disease

“…The microbiome is often disturbed in preterm born infants, which can increase the risk for tissue inflammation in these children. They emphasize that an improved understanding of tissue-resident immunity holds the potential to unearth novel targets of vaccination and enables individualized approaches to protect preterm born babies in the future [ 2 ] .…”