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

Abstract

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.

Sustained maternal antibody and cellular immune responses in pregnant women infected with Zika virus and mother to infant transfer of Zika‐specific antibodies

“…Our work complements the findings of these two groups and is the first to report transplacental ZIKV‐specific IgG transfer in the United States, in a low‐transmission population. Efficient transfer of maternal ZIKV‐specific IgG to infant circulation has been observed in the Brazilian population, 29 which is also corroborated in our study. We speculate that such maternal antibodies may have beneficial effects for the fetus and newborn.…”

“…We also demonstrate maternal to fetal transfer of ZIKV‐specific IgG in infant cord blood at the time of delivery. Recently, ZIKV‐specific and Dengue virus‐specific transplacental IgG transport has been reported in a cohort of mother/infant pairs from Brazil 29 . ZIKV‐specific IgG has been quantified in infant blood from another case‐control study of infants with microcephaly in Brazil 30 .…”

Congenital Zika Virus Infection in a Birth Cohort in Vietnam, 2017–2018

“…[26][27][28] High percentage of cord blood and neonate plasma samples positive for anti-Flavivirus IgG was observed, and it could be because of the passively transferred maternal IgG. 29 Increasing number of divergent ZIKV strains that highlight genetic variability is regarded as a potential limiting factor of the sensitivity of ZIKV qRT-PCR based diagnosis; therefore, a previous study suggested to use several qRT-PCR targets for diagnosis. 23 The 11 babies with confirmed CZI in this study had their plasma samples positive for qRT-PCR in at least one primer set.…”

The neonatal Fc receptor in mucosal immune regulation

“…This is exemplified by newborns that have inherited dengue virus‐specific IgG from the mother, which can bind to the closely related zika virus without neutralizing it. Instead, IgG‐opsonized zika virus can be transported across the placenta and lead to enhanced foetal viral infection 62 . Support for this has been given by in vitro experiments showing that serum from dengue‐immune humans enhanced translocation of zika virus across endothelial cells in an FcRn‐dependent manner, where transported virus was shown to be viable and able to infect target cells 63 …”