6dfi | pdb_00006dfi
Crystal structure of anti-Zika antibody Z021 bound to Zika virus envelope protein DIII
Structural highlights
FunctionA0A0U3FSM8_ZIKV Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Publication Abstract from PubMedZika 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. A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates.,Keeffe JR, Van Rompay KKA, Olsen PC, Wang Q, Gazumyan A, Azzopardi SA, Schaefer-Babajew D, Lee YE, Stuart JB, Singapuri A, Watanabe J, Usachenko J, Ardeshir A, Saeed M, Agudelo M, Eisenreich T, Bournazos S, Oliveira TY, Rice CM, Coffey LL, MacDonald MR, Bjorkman PJ, Nussenzweig MC, Robbiani DF Cell Rep. 2018 Nov 6;25(6):1385-1394.e7. doi: 10.1016/j.celrep.2018.10.031. PMID:30403995[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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