[PDF][PDF] A combination of two human monoclonal antibodies prevents Zika virus escape mutations in non-human primates
JR Keeffe, KKA Van Rompay, PC Olsen, Q Wang… - Cell reports, 2018 - cell.com
JR Keeffe, KKA Van Rompay, PC Olsen, Q Wang, A Gazumyan, SA Azzopardi…
Cell reports, 2018•cell.comZika 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 …
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 …
Summary
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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