Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigen-specific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics.
Author summary In 2015, a Zika virus (ZIKV) epidemic emerged in Latin America, where dengue virus (DENV) already was endemic. The ZIKV epidemic revealed an array of birth defects and neurodevelopmental abnormalities in newborns associated with maternal infection. ZIKV may now be co-endemic in Latin America with DENV. Antibodies transferred from mother to the fetus in pregnancy can protect newborns from infections in early life, before they are eligible for vaccination. Conversely, flavivirus-specific IgG transfer could mediate enhancement of DENV infections in early life, or transfer ZIKV immune complexes into the fetal compartment. As a first step in evaluating these potential outcomes, it is important to understand whether ZIKV infection in pregnancy and its associated placental pathology impacts the magnitude or types of IgG subpopulations that are transferred across the placenta. To test this, we assessed paired maternal and cord blood collected at delivery from mothers who presented with rash and/or fever in pregnancy during the ZIKV epidemic in Vitoria, Brazil. Of these, we classified 8 as ZIKV-infected based on virus detection and/or neutralization serology, and 12 as ZIKV-uninfected. Comparing ZIKV-infected and uninfected groups, we detected no difference in transfer efficiency of IgG targeting ZIKV, DENV, or routine vaccine antigens. These findings indicate that the magnitude of IgG transferred across the placenta was not deficient at the time of birth in the setting of maternal ZIKV infection. Sustained transplacental IgG transfer with ZIKV infection during pregnancy indicates that ZIKV exposure in utero should not impact maternal antibody mediated protection during early life. However, concern remains over potential risk of severe primary DENV infection in ZIKV-exposed infants in endemic regions, or whether ZIKV could access the fetal compartment via antibody-mediated transport. This passive antibody transfer in pregnancy is an important consideration for flavivirus vaccine and therapeutic development efforts.