Placental antibody transfer efficiency and maternal levels: specific for measles, coxsackievirus A16, enterovirus 71, poliomyelitis I-III and HIV-1 antibodies

Abstract

Maternal antibodies transported across the placenta can provide vital immunity against infectious pathogens for infants. We here examine maternal antibody (MA) levels and their association with neonatal antibody levels. Pregnant women of gestational age ≥35 weeks were enrolled at a Guangzhou China hospital and mother-infant paired sera were collected. Measles IgG antibody was detected using ELISA assay, neutralizing antibodies titers against coxsackievirus A16 (CA16), enterovirus 71 (EV71), PV I-III and HIV-1 were performed. 711 mother-infant pairs were enrolled and positive relationships for paired serums were found (r: 0.683–0.918). 81.6%, 87.0%, and 82.3% of mothers, and 87.3%, 72.7%, and 72.2% of newborns were positive for measles, CA16 and EV71 antibodies respectively. The highest Neonatal: maternal ratio (NMR) was found in measles (1.042) and the ratios for the other pathogens ranged from 0.84 to 1.00. Linear regressions showed that log(NMR) decreased by a factor of 0.04–15.43 as log(MA) levels increased. A second analysis restricted to maternal positive measles sera revealed that MA measles of was still inversely associated with NMR. Low NMR was found in high MA HIV + serums among 22 paired sera. MA levels appear to play a role determining transplacental antibody transfer; further study is needed to reveal the mechanism.

Fc Glycan-Mediated Regulation of Placental Antibody Transfer

“…The placenta preferentially transfers IgG antibodies (Vidarsson et al, 2014). Although FcRn binds to all IgG subclasses, differences in transfer efficiencies have been noted across the subclasses (IgG1 > 4 > 3 > 2) (Palmeira et al, 2012;Vidarsson et al, 2014;Wilcox et al, 2017) and across IgG1 populations (Fu et al, 2016), raising the possibility for FcRn-mediated preferential selection of IgG1 transfer. Thus, to begin to define the characteristics of antibodies that are preferentially transferred across the placenta, we aimed to define whether the transferred antibodies possessed any qualitative functional differences from those in mothers, focusing on pertussis-specific immunity.…”

“…Maternal immunization, aimed at enhancing maternal-to-fetal transfer of antibodies, has shown significant promise in boosting newborn immunity (Forsyth et al, 2015), providing a non-invasive strategy to enhance immunity in this vulnerable population. However, epidemiologic studies focusing on matched mother:fetus pairs have found that the extent of immunity transferred varies significantly by antigen (Fu et al, 2016;Palmeira et al, 2012). Specifically, while measles-specific antibodies are transferred efficiently (>100%), antibodies targeting other pathogens, including poliovirus and Coxsackie viruses, are less efficiently transferred (Fu et al, 2016).…”

“…However, epidemiologic studies focusing on matched mother:fetus pairs have found that the extent of immunity transferred varies significantly by antigen (Fu et al, 2016;Palmeira et al, 2012). Specifically, while measles-specific antibodies are transferred efficiently (>100%), antibodies targeting other pathogens, including poliovirus and Coxsackie viruses, are less efficiently transferred (Fu et al, 2016).…”

“…Given that FcRn binding occurs in the CH3 domain, IgG transport, and particularly antigen-specific IgG1 transport, should occur at the same rate. However, a transfer hierarchy exists across antigenspecific antibody subpopulations (Fu et al, 2016). Thus, other qualitative antibody features are likely to govern differential transfer of particular antibody populations.…”

FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies

“…These include the mechanism(s) governing preferential transfer of the IgG1 subclass and the variation of transfer efficiency that can occur based on IgG Fab specificity. Further, whether FcγRs have any role in transplacental IgG transport or whether specific post-translational modifications of IgGs can impact transfer through any mechanism are questions that have not been resolved (9)(10)(11)(12)(13)).…”