Cytomegalovirus-specific, high-avidity IgG with neutralizing activity in maternal circulation enriched in the fetal bloodstream

Abstract 

Background

Cytomegalovirus (CMV) is the major cause of congenital infection and disease leading to permanent birth defects. In about 35–40% of pregnant women with primary CMV infection, virus crosses the placenta, resulting in the birth of congenitally infected babies. In contrast, this happens in only 1–3% of seropositive women with strong CMV-specific humoral immunity. Whether CMV reaches the fetus and disseminates depends on the level of high-avidity antibodies in the maternal circulation and the passive immunity of the fetus.

Objectives and study design

To identify CMV infection in uncomplicated deliveries based on detection of viral DNA in placental biopsy specimens at term. To quantify CMV-specific IgG avidity, neutralizing titer, IgG1 concentration, and characterize the immunoblot profiles for CMV proteins in paired samples of placental and cord blood sera.

Results

In accord with earlier reports, CMV DNA was detected in 39% (11/28) of placentas with mean- to high-avidity CMV-specific IgG. In seropositive women, the concentration of antiviral antibodies, specifically IgG1, increased in the fetal bloodstream, and CMV neutralizing titers in maternal and fetal blood were comparable.

Conclusions

CMV-specific, high-avidity neutralizing antibodies from maternal circulation are transcytosed to the fetal bloodstream, contribute to suppression of viral replication in the placenta and could prevent congenital disease.

Abbreviations: CMV, cytomegalovirus, DMEM, Dulbecco's modified Eagle's medium, ELISA, enzyme-linked immunosorbent assay, gB, glycoprotein B, IE, immediate early, PCR, polymerase chain reaction

Keywords: Congenital CMV infection, Passive immunity, Neonatal Fc receptor, High-avidity IgG, Neutralizing titer