Maternal Immunization as a Strategy to Decrease Susceptibility to Infection in Newborn Infants

Benjamin Lindsey; Beate Kampmann; Christine Jones


Curr Opin Infect Dis. 2013;26(3):248-253. 

In This Article

Mechanisms Underlying the Principles of Maternal Immunization

Placental transfer of maternal immunoglobulin is restricted to IgG and confers short-term passive immunity to the newborn infant. Maternal IgA present in colostrum and breast milk complements protection derived through the placenta.

Maternal IgG is endocytosed within placental syncytiotrophoblast cells and is bound to the neonatal Fc receptor (FcRn) in the acidic environment of the endosome. IgG is released to the fetal side of the syncytiotrophoblast when exposed to physiological pH; it then passes through the villous stroma before crossing the fetal capillary epithelium and into the fetal circulation.[2]

Transplacental transfer of maternal IgG is affected by a number of factors that are important to consider in the context of maternal vaccination. The rate of transfer of maternal IgG to the fetus increases throughout gestation with maternal IgG first detected from 13 weeks gestation, however the majority of maternal IgG is transferred in the last 4 weeks of pregnancy.[3] The differential rate of transfer is an important determinant of the timing of maternal vaccination to ensure optimal transfer of antibody from mother to fetus. Transplacental transfer of antibody is an active process and can result in fetal concentrations of IgG that are greater than the maternal IgG concentration. This has been demonstrated with tetanus, pertussis and diphtheria-specific IgG.[4,5] Maternal vaccination can therefore ensure at least comparable protection in the infant as in the mother. Higher infant concentrations of IgG are desirable as they are associated with a longer duration of protection in the infant, thereby ensuring a narrow window of vulnerability prior to the protection conferred by active infant immunization. The concentration of fetal IgG positively correlates with the maternal IgG concentration until the infant FcRn receptor becomes saturated and unbound maternal IgG is digested by lysosomal enzymes within the endosome. IgG has different subclasses which cross the placenta with different efficiency; the reasons for this are unclear, but this may be related to variable affinities for the FcRn receptor. IgG1 is preferentially transferred, followed by IgG4, IgG3 and then IgG2.[2] Vaccines, such as tetanus, containing protein antigens elicit a predominantly IgG1 and IgG3 response and therefore vaccine-specific IgG is transferred with greater efficiency than specific IgG to polysaccharide vaccine antigens, such as those contained in the pneumococcal polysaccharide vaccine, which elicit a predominantly IgG2 response.[6] In the presence of maternal HIV or malaria, the transplacental transfer of specific IgG is reduced, a factor which may need to be considered when evaluating the efficacy of maternal vaccination in high burden settings.[1,7] It has been postulated that maternal HIV specific antibodies block FcRn receptors thereby reducing placental transfer of vaccine-specific antibodies, and that malaria exerts its effect through pathological damage to the placenta however, the mechanisms are not known.[8,9]