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Convalescent Serum Prevents Zika Infection and Microcephaly in Mice
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease. Recent ZIKV epidemics are linked to Guillain-Barre syndrome in adults and microcephaly in fetuses. Specific treatments or vaccines for ZIKV are not available, so to develop candidate therapeutic agents against ZIKV is extremely urgent.
Scientists from XU Zhiheng’s group at the Institute of Genetics and Developmental Biology, Chinese Academy of Sciences found that convalescent serum can prevent Zika virus replication and microcephaly in offspring in a recent research.
They firstly inspected the in vitro neutralizing activity of the convalescent serum from a donor who recovered from ZIKV infection 2 months before by a standard plaque reduction neutralization test (PRNT) using BHK21 cells and PRNT50 against ZIKV was calculated to 1:161 by non-linear regression analysis.
They next determined whether convalescent serum had therapeutic activity in vivo. They injected approximately 650 PFU ZIKV into the cerebroventricular space of embryonic day 13.5 (E 13.5) brains. Then, the dams were administered vehicle control, healthy human serum or convalescent serum once daily on day 1 and 2 after the brains of embryos were infected with ZIKV. Fetuses at E18.5 from vehicle control or healthy human serum treated dams showed high levels of zika virus and cell death in the fetal brains. In comparison, fetuses from convalescent serum treated dams had dramatically reduced levels of zika virus and cell death.
Furthermore, they found that convalescent serum can prevent microcephaly induced by ZIKV infection. In addition, the thinning of the cortical plate and ventricular zone/subventicular zone, dysregulation of NPC cell cycle and proliferation which was observed in the infected fetal brains were also effectively rescued by the serum treatment.
The results demonstrated that passive transfer of convalescent serum containing high-titer neutralizing antibodies can protect against fetal infection and microcephaly. And the results highlight the potential application of monoclonal antibodies in pregnant women in the endemic regions.
This study entitled “Transfer of convalescent serum to pregnant mice prevents zika virus infection and microcephaly in offspring” was published online in Cell Research. This work was supported by grants from National Natural Science Foundation of China, the National Basic Research Program and National Key Research Program of China.
Convalescent serum protects embryos from ZIKV brain infection and microcephaly. (Image by IGDB)
Dr. XU Zhiheng