Short-Lived Zika Virus-Specific Antibodies in Infants: Findings from a Translational Macaque Model

Abstract Background In utero Zika virus (ZIKV) infection is a significant public health threat for infants as it can be vertically transmitted from mother to fetus, resulting in several health problems. Prolonged maternal viremia sometimes occurs in pregnant women with ZIKV infection. We hypothesize that mothers with prolonged viremia will be more likely to vertically transmit ZIKV to their fetuses. To evaluate this hypothesis, we developed a rhesus macaque pregnancy model of ZIKV infection, where some days have prolonged viremia (>10 days) and others have quickly cleared viremia (<10 days). Because the diagnosis of fetal ZIKV infection in newborns is challenging given the transient nature of ZIKV RNA viremia, we use infant-produced ZIKV-specific IgG as a marker of ZIKV vertical transmission. Here, we used a rhesus macaque model to define the association between longitudinal ZIKV-specific IgG antibody titers in infants and duration of maternal viremia. Methods Pregnant dams were inoculated in the first trimester, and their infants (n=8) were monitored for 12 months. ZIKV-specific IgG titers were measured in ZIKV-exposed infant serum samples using a whole virion ELISA at 1, 3, 6, 12, 18, 24, 30, and 36 months of age. Optical density was detected at 450nm on a SpectraMax M5e plate reader and IgG binding antibody curves were generated using R studio. Samples were below the limit of detection if they had EC90 values lower than the lowest serum dilution. Results One of the eight infants displayed ZIKV-specific IgG titers at 12 months of age with undetectable ZIKV-specific IgG before 12 months of age, suggesting that these infants were infected in utero and produced their own ZIKV-specific IgG. This infant was born to a dam with a short duration of plasma viremia. The remaining seven infants displayed measurable ZIKV-specific IgG in the first 3 months of life and nothing after that point, indicating the presence of maternal antibody and no infant-specific antibody. There was no apparent association between maternal viremia duration and the presence of infant-produced ZIKV-specific IgG. Conclusion ZIKV vertical transmission was confirmed in 1 of 8 pregnancies, and that case did not have a longer viremia compared to the other pregnancies. This indicates that either the rate of vertical transmission is not high in this macaque model, or that diagnostic methods for in utero infection with ZIKV are limited. We have additional pregnancies to complete antibody testing for in our cohort (10 additional pregnancies) and will learn more about this diagnostic method in these future studies.