Human Monoclonal Antibodies Prevent Congenital Transfer of Zika Virus in Mice
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By Gerald M. Slutzky, PhD Posted on 16 Nov 2016 |
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Image: A researcher holds a tray of Zika virus growing in animal cells. Researchers have identified a human antibody that prevents, in pregnant mice, the fetus from becoming infected and the placenta from being damaged (Photo courtesy of Huy Mach, Washington University School of Medicine).
A class of human monoclonal antibodies specific for Zika virus was found to prevent transfer of the virus from pregnant mice to the fetus as well as protecting adult mice from infection.
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, investigators at Washington University School of Medicine (St. Louis, MO, USA) and at Vanderbilt University School of Medicine (Nashville, TN, USA) isolated a panel of human monoclonal antibodies (mAbs) from a group of 29 subjects who had prior ZIKV infections.
The investigators reported in the November 7, 2016, online edition of the journal Nature that some of the mAbs recognized diverse epitopes on the viral envelope (E) protein and exhibited potent neutralizing activity. One of the most inhibitory mAbs, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African, Asian, and American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface.
The therapeutic efficacy of ZIKV-117 was evaluated in pregnant and non-pregnant mice. Results revealed that treatment with the mAb markedly reduced tissue pathology, placental, and fetal infection, and mortality in mice.
“This is the first antiviral that has been shown to work in pregnancy to protect developing fetuses from Zika virus,” said co-senior author Dr. Michael Diamond, professor of medicine at Washington University School of Medicine. “This is proof of principle that Zika virus during pregnancy is treatable, and we already have a human antibody that treats it, at least in mice. We know that Zika can persist in certain parts of the body, such as the eyes and the testes, where it can cause long-term damage, at least in mice. We showed that the antibody can prevent disease, and now we want to know whether it can clear persistent infection from those parts of the body.”
Related Links:
Washington University School of Medicine
Vanderbilt University School of Medicine
Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that can cause severe disease, including congenital birth defects during pregnancy. To develop candidate therapeutic agents against ZIKV, investigators at Washington University School of Medicine (St. Louis, MO, USA) and at Vanderbilt University School of Medicine (Nashville, TN, USA) isolated a panel of human monoclonal antibodies (mAbs) from a group of 29 subjects who had prior ZIKV infections.
The investigators reported in the November 7, 2016, online edition of the journal Nature that some of the mAbs recognized diverse epitopes on the viral envelope (E) protein and exhibited potent neutralizing activity. One of the most inhibitory mAbs, ZIKV-117, broadly neutralized infection of ZIKV strains corresponding to African, Asian, and American lineages. Epitope mapping studies revealed that ZIKV-117 recognized a unique quaternary epitope on the E protein dimer–dimer interface.
The therapeutic efficacy of ZIKV-117 was evaluated in pregnant and non-pregnant mice. Results revealed that treatment with the mAb markedly reduced tissue pathology, placental, and fetal infection, and mortality in mice.
“This is the first antiviral that has been shown to work in pregnancy to protect developing fetuses from Zika virus,” said co-senior author Dr. Michael Diamond, professor of medicine at Washington University School of Medicine. “This is proof of principle that Zika virus during pregnancy is treatable, and we already have a human antibody that treats it, at least in mice. We know that Zika can persist in certain parts of the body, such as the eyes and the testes, where it can cause long-term damage, at least in mice. We showed that the antibody can prevent disease, and now we want to know whether it can clear persistent infection from those parts of the body.”
Related Links:
Washington University School of Medicine
Vanderbilt University School of Medicine
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