6DFI

Crystal structure of anti-Zika antibody Z021 bound to Zika virus envelope protein DIII

Summary for 6DFI

• Entry DOI: 10.2210/pdb6dfi/pdb
• Descriptor: anti-Zika antibody Z021, Heavy Chain, anti-Zika antibody Z021, Light Chain, Zika virus envelope protein DIII, ... (4 entities in total)
• Functional Keywords: antibody, fab, zika, dengue, recurrent, neutralizing, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 60538.82

Authors

Keeffe, J.R.,Bjorkman, P.J. (deposition date: 2018-05-14, release date: 2018-10-24, Last modification date: 2018-11-14)

Primary citation

Keeffe, J.R.,Van Rompay, K.K.A.,Olsen, P.C.,Wang, Q.,Gazumyan, A.,Azzopardi, S.A.,Schaefer-Babajew, D.,Lee, Y.E.,Stuart, J.B.,Singapuri, A.,Watanabe, J.,Usachenko, J.,Ardeshir, A.,Saeed, M.,Agudelo, M.,Eisenreich, T.,Bournazos, S.,Oliveira, T.Y.,Rice, C.M.,Coffey, L.L.,MacDonald, M.R.,Bjorkman, P.J.,Nussenzweig, M.C.,Robbiani, D.F.
A Combination of Two Human Monoclonal Antibodies Prevents Zika Virus Escape Mutations in Non-human Primates.
Cell Rep, 25:1385-1394.e7, 2018

PubMed Abstract: 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.

PubMed: 30403995
DOI: 10.1016/j.celrep.2018.10.031

Experimental method

X-RAY DIFFRACTION (2.48 Å)