Vertically Transferred Immunity in Neonates: Mothers, Mechanisms and Mediators

Abstract

Over the last years, an increasing number of outbreaks of vaccine-preventable infectious diseases has been reported. Besides elderly and immunocompromised individuals, newborns and small infants are most susceptible to infections, as their immune system is still immature. This vulnerability during infancy can be mitigated by the transplacental transfer of pathogen-specific antibodies and other mediators of immunity from mother to the fetus during pregnancy, followed postnatally by breast milk-derived immunity. Since this largely antibody-mediated passive immunity can prevent the newborn from infections, neonatal immunity depends strongly on the maternal concentration of respective specific antibodies during pregnancy. If titers are low or wane rapidly after birth, the protection transferred to the child may not be sufficient to prevent disease. Moreover, emerging concepts propose that mothers may transfer active immunity to the newborns via vertical transfer of pathogen-specific T cells. Overall, a promising strategy to augment and prolong neonatal immunity is to vaccinate the mother before or during pregnancy in order to boost maternal antibody concentrations or availability of specific T cells. Hence, a large number of pre-and postconceptional vaccine trials have been carried out to test and confirm this concept. We here highlight novel insights arising from recent research endeavors on the influence of prenatal maternal vaccination against pathogens that can pose a threat for newborns, such as measles, pertussis, rubella and influenza A. We delineate pathways involved in the transfer of specific maternal antibodies. We also discuss the consequences for children's health and long-term immunity resulting from an adjustment of prenatal vaccination regimes.

Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health

“…The factors most unique to early life that shape humoral responses include maternally transferred antibodies and colonization of the newborn gut microbiota. Due to the limitations to generating antibody responses in early life, neonates rely heavily on passive maternal antibody transfer for protection against infections [reviewed in ( 116 )]. Transplacental IgG transfer, mediated by the neonatal Fc receptor (FcRn), begins during the second trimester and increases throughout gestation ( 117 ).…”

Maternal Immunization: Nature Meets Nurture

“…The MMCs express non-inherited maternal antigens and can persist in the offspring long-term, detectable even up to 62 years postnatally. A considerable proportion belong to the immune compartment, particularly T-cells or tissue-resident memory cells (Albrecht and Arck, 2020); it is estimated that up to 1 in 5,000 peripheral blood mononuclear cells may be of maternal origin (Kinder et al, 2017a). In a previous case of a human infant with severe combined immunodeficiency, activated CD8 + T-cells and IFN-γ-secretion were detected in response to EBV infection; these cells displayed a maternal genotype (Touzot et al, 2012).…”

“…In addition, maternal cells are increasingly thought to migrate transplacentally to offspring at low frequencies ( Kinder et al, 2015 ). Further pathogen-specific immunity may, therefore, be conferred to the newborn, enhancing protection already delivered by maternal antibody ( Albrecht and Arck, 2020 ; Kollmann et al, 2020 ). This is based on the principle that bidirectional transfer can occur during pregnancy, with seeding of genetically foreign maternal and fetal cells, known as ‘microchimeric cells.’ The biological function and molecular phenotypes of these rare fetal (FMC) and maternal (MMC) microchimeric cells is poorly understood.…”

Immune maturation and modulation in childhood allergies : Aspects of epigenetic, mucosal and systemic immune mediators in allergy development and prevention

“…15,33,145 Prenatally, the transplacental transmission of dietary nutrients and metabolites as well as antigens and antibodies supplies the foetus not only with building blocks for general growth, but also environmental cues for induction of foetal immune responses. Transplacental communication of IgG-antibodies, either as is or complexed with antigens of microbial or allogeneic origin, is enabled through transport by the neonatal Fc receptor 146 , which by endocytotic processes transports and releases the contents into the foetal circulation in the placenta. 147 This begins early in the second trimester, enabling both the passage of passive immunity from the mother, while at the same time influencing immune maturation.…”