Association of Viral Control and Maternal Antibody Titers in Congenital Zika Virus Infection

Abstract

Abstract Background Exposure to Zika virus (ZIKV) in utero can result in a wide spectrum of outcomes, ranging from asymptomatic to severe neurological defects or fetal demise. The presence of virus in the fetus or in the mother’s blood for a prolonged period of time may lead to worse outcomes, which means that limiting the duration of fetal exposure to virus may improve outcomes. One factor that may be related to control of maternal viremia and presence of virus in the fetus is the maternal IgG antibody response. We utilized a rhesus macaque model of prenatal ZIKV to quantify the viral RNA present in the maternal blood and maternal-fetal interface (MFI) tissues and determine the association of viral RNA loads with maternal IgG antibody titers over time. Methods Dams were infected with either African lineage ZIKV-DAKAR (n=9) or Asian lineage ZIKV-PRVABC59 (PR, n=10) isolate in the first trimester, then all fetal and MFI tissues were removed either 7 or 14 days post-infection (dpi) and viral RNA loads were measured. Maternal plasma was tested for viral RNA and IgG throughout pregnancy. Results A greater proportion of animals infected with the DAKAR isolate had viral RNA present in the MFI tissues compared with the animals infected with the PR isolate, at both 7 and 14 dpi. DAKAR animals also tested positive for ZIKV-specific IgG at 14 dpi or earlier, while IgG was typically negative at 14 dpi for PR animals. Viral RNA was detected in the fetal and MFI tissues in a higher proportion of dams that still had ZIKV RNA positive plasma at 14 dpi had viral RNA. We found no difference in IgG antibody titers between dams that were ZIKV positive or negative at 14 dpi. Conclusions The presence of ZIKV in the MFI tissues and earlier detection of ZIKV-specific maternal IgG responses were both associated with the DAKAR isolate, suggesting that it may be a more virulent isolate. A higher proportion of dams that had virus in their plasma at 14 dpi also had virus present in the fetal and MFI tissues, but there was no difference in long term IgG response within either isolate between animals that tested positive or negative at 14 dpi. This suggests that the dam clearing viral RNAfrom their plasma by 14 dpi may impact whether or not the virus infects the MFI tissues, but that maternal IgG response likely does not play a role in this difference.