One caveat to the data presented from the placenta is that we only sampled 3 sections from each placenta and may have missed computer virus present in other sections of the placenta. utero Zika computer virus (ZIKV) contamination causes devastating congenital outcomes in 510% of fetuses [1,2]. Even though ZIKV has receded from public attention, the risk of future outbreaks looms large. TheAedes aegyptimosquito vector that primarily transmits ZIKV is found in 61 countries where the computer virus has never been documented [3]. Even in countries with documented ZIKV transmission, seroprevalence is often low (~10%) [4,5]. Together, these data suggest that there are numerous ZIKV-naive individuals at risk for future infections. In addition, durability of ZIKV immunity is usually unknown for individuals living in regions that have already experienced outbreaks. If ZIKV outbreaks mimic those of the genetically related dengue computer virus (DENV), endemo-epidemic outbreaks are likely, motivating the development of medical countermeasures that could be deployed quickly in future outbreaks [6]. To prevent congenital Zika syndrome (CZS), which includes conditions like microcephaly, congenital joint contractures, ocular abnormalities, and auditory deficits, it is important to establish treatment and prevention approaches now. There are no FDA-approved therapies to treat or prevent ZIKV contamination. Promising vaccines have made it through phase I and into phase II clinical trials, but are stalled due to lack of ongoing ZIKV transmission [7,8]. Vaccination before conception in a pregnant rhesus macaque model reduced CP 471474 the risk of CZS and appeared to prevent detectable computer virus in the fetus, despite the fact that it did not prevent maternal viremia in over half of the animals [9]. However, many ZIKV vaccine candidates use a live attenuated computer virus backbone, which is usually often contraindicated for use during pregnancy due to a theoretical risk to the fetus [10,11]. Safe biological products that can be used early during pregnancy to prevent or treat ZIKV and mitigate the impact of congenital effects would be especially desirable. Hyperimmune globulin (HIG) is usually one such biological product. HIG is usually produced by isolating mature, high-affinity IgG antibodies from individuals naturally exposed to a pathogen. Hyperimmune globulin is usually FDA-approved to treat Varicella Zoster computer virus contamination (VARIZIG), Rh-incompatibility (Rhophylac, WinRho), and other conditions such as immune thrombocytopenia (WinRho SDF) in pregnant women [12,13]. Hyperimmune globulin has also been tested to treat other emerging infectious diseases for which treatment options are limited such as H1N1 influenza, Ebola, and SARS-CoV-2 [1416]. Lastly, HIG contains both neutralizing and binding antibodies that may mediate alternative virus-specific mechanisms to control viral replication, such as antibody-dependent cellular cytotoxicity (ADCC). Fortuitously, antibodies (Abs), especially neutralizing antibodies (NAbs), are Rabbit Polyclonal to Collagen III CP 471474 considered the primary correlate of immune protection for ZIKV based on protective vaccines tested in rhesus macaques [17,18]. Immunoglobulins isolated from vaccinated animals were sufficient to protect naive animals from ZIKV contamination [17]. We have shown that PRNT50 values of >2.75 Log10 serum dilution, in animals exposed to ZIKV approximately 2 years before rechallenge, were sufficient for protection from re-infection [19]. Similarly, Abbink, et al. showed that a 50% microneutralization log titer of 2.02.1 following vaccination was the required threshold for protection in their study [18]. Lastly, monoclonal antibodies (mAbs) have been tested as passive immunization in nonhuman primates. One study showed that mAbs were effective at blunting viral replication, but ZIKV can rapidly develop escape mutations in the presence of a single Ab thereby necessitating treatment with at least two different mAbs [20]. Even with two mAbs, viremia was not prevented in this study. In another study testing a cocktail of 3 mAbs 24 hours before contamination, 4 of 4 animals were guarded from detectable computer virus in the blood. In pregnant rhesus macaques, this cocktail of mAbs was provided at 3 days post-infection and cleared computer virus from the serum in 2 of 3 animals, but computer virus was still detectable in the amniotic fluid of CP 471474 two of the animals, though not in the fetus at the time of birth a few weeks later [21]. In this study, we treat eight pregnant Indian-origin rhesus macaques with either human-derived ZIKV-specific IgG (ZIKV-IG) or human-derived placebo-IG one day after ZIKV contamination around gestational day (GD) 45 (end of first trimester). In macaques each trimester is usually ~55 days and full term is considered 165 days. We monitor plasma viral load in the dams, fetal growth, pharmacokinetics of the infused ZIKV-IG, vertical transmission, birth defects, and histopathology in the infant at the time of birth by cesarean section at ~GD 155. ZIKV-IG treatment dramatically reduces plasma ZIKV viremia in the dams after infusion while placebo-IG does not. No ZIKV-associated birth defects nor ZIKV RNA are found in the infants at the time of birth in either.