Antibody decreases Zika virus levels and fetal transmission [PreClinical]

1. Antibodies were isolated from patients with prior Zika virus infection and one specific antibody, ZIKV-117, decreased fetal transmission of Zika virus as well as viral replication in mice.

2. ZIKV-117 was efficacious at neutralizing the Zika virus when administered prophylactically and after virus exposure.

Evidence Rating Level: 2 (Good)

Study Rundown: Zika virus is known to cause microcephaly in fetuses and newborns as well as induce Guillain-Barré Syndrome in adults. Despite the pathogenic effects of Zika virus, there is currently no treatment or vaccine for this virus. Because of this, researchers in this study used serum from patients who had been infected with Zika virus and studied the potential use of their antibodies on eradicating the virus. The most inhibitory antibody, ZIKV-117, was tested in mice to determine its effects on viral eradication and fetal transmission of the virus.

First, mice were inoculated with the virus and then given a single dose of ZIKV-117. One dose of the antibody was able to significantly increase the survival of the mice. Next, knockout mouse models of placental transfer of Zika virus (Ifnar1^-/- mice) were treated with ZIKV-117 and then infected with Zika virus. Reduced viral levels were noted in the maternal brain and serum. The pups also demonstrated a significant increase in survival compared to those that did not receive antibody. Similar results were seen in wildtype (WT) mice given anti-Ifnar monoclonal antibody (mAb) to mimic the human response to Zika virus. There was a lack of viral RNA in the placenta of the mice given ZIKV-117, and this antibody was able to reduce the placental transfer of Zika virus.

Although the ability of these results to be directly translated to humans is currently unclear, these results provide strong evidence for an antibody-based approach to the development of an efficacious treatment for Zika virus disease. Further, this approach could be efficacious as a prophylactic and post-exposure treatment for pregnant mothers.

Click to read the study in Nature

Relevant Reading: Zika Virus: Medical Countermeasure Development Challenges

In-Depth [animal study]: WT male mice were administered anti-Ifnar1 mAb and then given a mouse-adapted viral strain of ZIKV-Dakar. These mice were then treated with either 100 µg ZIKV-117 one day after infection or 250 µg five days after infection, with hCHK-152 given as an isotype control. Both treatment groups showed a significant increase in survival compared to the control (p<0.05), with 100% survival seen in the mice treated after day one.

Ifnar^-/- pregnant dams were then treated with either ZIKV-117 or the isotype control at embryo day (E) 5.5 and then inoculated with ZIKV-Brazil at E6.5. The pups born showed a significant increase in survival (p<0.0001), with almost a 100% survival rate. In addition, there was a significant decrease in viral load in the maternal brain and serum (p<0.05).

Finally, the effect of the administration of ZIKV-117 before exposure to the Zika virus was tested in pregnant dams given anti-Ifnar1 mAb. Hematoxylin and eosin staining of the placenta revealed decreased placental damage and less trophoblast cell death. Fetal size was also found to be increased, and in situ hybridization showed an absence of viral RNA in the placenta of the treated animals. Similar results were obtained when ZIKV-117 was administered as a treatment after Zika virus exposure.

Image: PD

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