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.

Keywords: FcRn; blunting; breastfeeding; influenza; maternal vaccination; measles; pertussis; rubella.

FIGURE 1

Overview of maternal immunity and recommended vaccinations before, during and after pregnancy as well as consequences for maternal and children’s health.

FIGURE 2

Mechanisms of antibody transfer via placenta and breast tissue. Top: Circulating IgG antibody is taken up into the syncytiotrophoblast cell, where two IgG molecules per FcRn bind at the inner membrane of the acidic endosome. Upon opening of the endosome at the basolateral side of the cell facing the fetal circulation, FcRn releases the IgG molecules due to the increased pH and can then be recycled to perform another transport cycle. Bottom: The joining chain of the dimeric IgA molecule is bound by the polymeric Ig-receptor (pIgR) and both are internalized via endocytosis. At the apical membrane, secretory IgA (sIgA) is being released to the breast milk, as the secretory component of pIgR remains bound to the IgA antibody.

FIGURE 3

Upon exposure of the neonate to vaccine antigens, the antigen is recognized by its specific B cell receptor (BCR). If maternal antibodies are present in the child’s circulation, they bind to the vaccine antigen as well as to the Fc-receptor FcRIIB that is also expressed on B cells. Thus, a cross-link between BCR and FcRIIB is formed, which inhibits antibody production of the B cell in response to antigen recognition.