Human Anti-HIV-1 gp120 Recombinant Antibody (clone 3bnc117) (CAT#: PABL-163)

Figure 1 Pharmacokinetics of 3BNC117 in healthy and HIV-1-infected individuals

a. Diagrammatic representation of the study. Time of 3BNC117 infusion indicated by the red arrow, and sampling for 3BNC117 serum levels, HIV-1 viral load, CD4+/CD8+ counts and env sequencing indicated below. b. Antibody decay measured in TZM.bl assays (solid lines) and ELISA (dotted lines). Mean values and SEM for uninfected individuals (3 per group) are shown in blue and for HIV-1-infected individuals (2–5 per group) in red. Light gray indicates lower level of accuracy by the ELISA assay and dark gray by the TZM.bl assay. Open circles indicate levels lower than the accuracy threshold.

Caskey, M., Klein, F., Lorenzi, J. C., Seaman, M. S., West Jr, A. P., Buckley, N.,... & Horwitz, J. A. (2015). 3BNC117 a broadly neutralizing antibody suppresses viremia in HIV-1-infected humans. Nature, 522(7557), 487.

Figure 2 HIV-1 viral load measurements

3BNC117 dose indicated in red. Plots (left-hand column) show absolute VLs in HIV-1 RNA copies/ml (y-axis) vs. time in days after infusion (x-axis; left panel). Log10 changes (right-hand column) in VL from day 0. Red line illustrates the average (LS-mean, by mixed-effect linear model). Individual subjects are indicated on the right side. Subjects 2E1-5 were pre-screened for 3BNC117-sensitivity. At 30 mg/kg dose level, the change in viremia was significant (p= 0.004, <0.001, <0.001, <0.001, 0.011 at days 4, 7, 14, 21, and 28, respectively) when compared to all available pretreatment values.

Caskey, M., Klein, F., Lorenzi, J. C., Seaman, M. S., West Jr, A. P., Buckley, N.,... & Horwitz, J. A. (2015). 3BNC117 a broadly neutralizing antibody suppresses viremia in HIV-1-infected humans. Nature, 522(7557), 487.

Figure 3 3BNC117 sensitivity, changes in viremia, and 3BNC117 levels

3BNC117 dose is indicated on the top of the graphs. The left y-axis shows log10 change in viremia from baseline, and right y-axis shows antibody level measured in ELISA. Blue line reflects change in VL and dotted gray line antibody level. Numbers indicate IC50s for 3BNC117 of autologous viral isolates measured by TZM.bl assay, color-coded as indicated on the top right.

Caskey, M., Klein, F., Lorenzi, J. C., Seaman, M. S., West Jr, A. P., Buckley, N.,... & Horwitz, J. A. (2015). 3BNC117 a broadly neutralizing antibody suppresses viremia in HIV-1-infected humans. Nature, 522(7557), 487.

Figure 4 (D–F) ELISA assays to determine dual specificity of the 3BNC117/10-1074 biNAb.

(D) Competition ELISA with increasing concentrations of each of the parental bNAbs or a mixture (1:1) of the two bNAbs to determine dual specificity of the biNAb. (E) The 3BNC117/10-1074 biNAb and the 3BNC117 and 10-1074 bNAbs were immobilized to gp140-coated microtiter plates and detected using Fc domain- or light-chain (κ or λ) subclass-specific secondary IgG. The biNAb was detected with both the anti-kappa and anti-lambda secondary antibodies, whereas 3BNC117 and 10-1074 were detected only with anti-kappa or anti-lambda, respectively.

Bournazos, S., Gazumyan, A., Seaman, M. S., Nussenzweig, M. C., & Ravetch, J. V. (2016). Bispecific anti-HIV-1 antibodies with enhanced breadth and potency. Cell, 165(7), 1609-1620.

Figure 5 (G) In vitro neutralization breadth and potency plot of 3BNC117/10-1074 IgG1 biNAb against an extended (120 strain) multiclade virus panel.

Neutralization activity of their respective parental IgG1 bNAbs was included for comparison. The 3BNC117/10-1074 IgG1 biNAb exhibited marked reduction in neutralization potency compared to the activity of a mix of their parental mAbs (determined based on the activity of the most potent parental mAb for a given virus strain)

Bournazos, S., Gazumyan, A., Seaman, M. S., Nussenzweig, M. C., & Ravetch, J. V. (2016). Bispecific anti-HIV-1 antibodies with enhanced breadth and potency. Cell, 165(7), 1609-1620.

Figure 6 In vitro neutralization breadth and potency plots of different anti-Env bNAb expressed as IgG1 or IgG3C- hinge variants. In vitro neutralization was assessed by TZMbl assay against an extended multiclade virus panel.

Bournazos, S., Gazumyan, A., Seaman, M. S., Nussenzweig, M. C., & Ravetch, J. V. (2016). Bispecific anti-HIV-1 antibodies with enhanced breadth and potency. Cell, 165(7), 1609-1620.

Figure 1 Anti-HIV-1 gp120 Antibody (PABL-163) in WB

Western blot analysis of PABL-163 was performed with HIV-1 gp120 Protein.

Figure 2 Anti-HIV-1 gp120 Antibody (PABL-163) in ELISA

ELISA analysis of PABL-163 was performed by coating with HIV-1 gp120 Protein.

Figure 3 Anti-HIV-1 gp120 Antibody (PABL-163) in Dot Blot

Dot Blot analysis of PABL-163 was performed by coating with HIV-1 gp120 Protein.