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A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates
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Nov 06 2018
Source: Cell Rep. 25(6):1385-1394.e7 -
Alternative Title:Cell Rep
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Description:Zika virus (ZIKV) causes severe neurologic complications and fetal aberrations. Vaccine development is hindered by potential safety concerns due to antibody cross-reactivity with dengue virus and the possibility of disease enhancement. In contrast, passive administration of anti-ZIKV antibodies engineered to prevent enhancement may be safe and effective. Here, we report on human monoclonal antibody Z021, a potent neutralizer that recognizes an epitope on the lateral ridge of the envelope domain III (EDIII) of ZIKV and is protective against ZIKV in mice. When administered to macaques undergoing a high-dose ZIKV challenge, a single anti-EDIII antibody selected for resistant variants. Co-administration of two antibodies, Z004 and Z021, which target distinct sites on EDIII, was associated with a delay and a 3- to 4-log decrease in peak viremia. Moreover, the combination of these antibodies engineered to avoid enhancement prevented viral escape due to mutation in macaques, a natural host for ZIKV.
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Pubmed ID:30403995
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Pubmed Central ID:PMC6268006
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Funding:R01 AI037526/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; UM1 AI100663/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; T32 AI070084/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; P51 OD011107/ODCDC CDC HHS/Office of the Director/United States ; U19 AI057229/NIAID NIH HHS/National Institute of Allergy and Infectious Diseases Extramural Activities/United States ; ... More +
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