Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: (A) ZKA190 was tested for neutralization of four strains of ZIKV, as determined by the percentage of infected Vero cells in the presence of increasing amounts of mAbs. Data are representative of at least two independent experiments.

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques: Neutralization, Infection

Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: (A) Cartoon representation of the 12 lowest-energy NMR structures of ZIKV DIII, with residues affected by ZKA190 binding in red. Flexibility in the N terminus of the construct is apparent.

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques: Binding Assay, Construct

Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: (A) Dynamic light scattering experiments measuring the hydrodynamic size of the virus complexes shows ZKA190 IgG aggregates ZIKV at IgG:virion molar ratio of ≥33:1. The neutralization activity of antibody correlates with the formation of virus-antibody aggregates. The neutralization is expressed as the log10-transformed fold-reduction of the virus titer compared to the virus-only control.

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques: Virus, Neutralization, Activity Assay, Transformation Assay, Control

Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: (A to D) ZKA190 is strongly protective against ZIKV infection when administered prophylactically to mice (A129 in (A) and AG129 in (C, D)) challenged with a lethal dose of ZIKV strain MP1745 (A, B) or Nica 2–16 (C, D). Experiments used N=4–8 mice per group. (A, C) Kaplan-Meier survival curves are shown. Significance was determined using the Mantel-Cox log-rank test. Panel A: ZKA190 at 5, 1 and 0.2 mg/kg versus Ctr mAb, P = 0.0031; ZKA190 at 0.04 mg/kg versus Ctr mAb, P = 0.0116; ZKA190-LALA at 5, 1, 0.2 and 0.04 mg/kg versus Ctr mAb, P = 0.0031. Panels C: ZKA190 and ZKA190 LALA at 1 mg/kg versus Ctr mAb, P = 0.0091; ZKA190 at 0.02 mg/kg versus Ctr mAb, P = 0.0035; ZKA190-LALA at 0.04 mg/kg versus Ctr mAb, P = 0.0142. (B, D) Morbidity score of mice monitored over a 14–15 day period (two different scoring methods were used; see (Dowall et al., 2016) for (B) and (Orozco et al., 2012) for panel D). Control mAb is MPE8 mAb (A, specific for RSV F protein (Corti et al., 2013)) and a human IgG polyclonal isotype control (C).

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques: Infection, Control

Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: (A) Superposition of the structures of the Fabs E16 (orange, PDB 1ZTX), E106 (cyan, PDB 4L5F), ZV23 (blue, PDB 5GZR) and ZK67 (purple, PDB 5KVG) onto DIII of ZKA190-E protein cryoEM structure.

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques:

Journal: Cell

Article Title: A human bi-specific antibody against Zika virus with high therapeutic potential

doi: 10.1016/j.cell.2017.09.002

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: However, due to the orientation of the Fabs, only the sites (cyan dotted circles) around the 5-fold and the 3-fold vertices can accommodate bivalent binding of a full IgG. (C) Molecular Dynamics (MD)-based atomic model of the full ZKA190 IgG (green) bridging across two neighboring E proteins on the viral surface (gray).

Techniques: Virus, Recombinant, SYBR Green Assay, Incubation, Mouse Assay, Software