Functional characterization of multidonor class antibodies.

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Presentation transcript:

Functional characterization of multidonor class antibodies. Functional characterization of multidonor class antibodies. (A and B) mAbs belonging to the multidonor VH6-1, VH1-18+ DH3-9, and VH1-18 QXXV classes or control antibodies were tested for binding to full-length recombinant HA or the stabilized stem of the indicated influenza strains (A) or neutralization in a microneutralization assay with the indicated strains (B). Full influenza strain names are detailed in Materials and Methods. Antibodies in bold were published previously (24) and shown for comparison. Control antibodies were previously characterized as group 1 stem binding (CR6261) (17), group 2 stem binding (CR8020) (21), or group 1 and group 2 stem binding (CR9114) (2). All other antibodies were cloned from B cells isolated after H7N9 vaccination. In (A), binding of each antibody to each strain is color-coded according to the AUC of the titration curve as indicated in the color legend. In (B), the mAbs are color-coded according to the microneutralization IC50 for each strain, as indicated in the legend. Actual values are in table S4. Representative data are shown from at least two independent experiments. (C) Mice were passively administered with the indicated antibody (5 mg/kg) (10 mice per group) 24 hours before infection with A/Anhui/01/2013 (H7N9) or A/California/07/2009 (H1N1) as indicated. As a control, one group received VRC01 IgG, an HIV-specific antibody. Mice were euthanized when they reached 80% of their initial weight. The left graph shows the Kaplan-Meier survival curve. There was greater survival in all groups that received an HA stem–binding antibody (P ≤ 0.001, Fisher’s exact test) compared to the control group. The middle graph shows the percent weight loss over time with each line representing one mouse. On the right, the percent weight loss is shown for animals in each group on the last day when all animals infected with that strain had a recorded weight. The weight loss is statistically lower (P < 0.0001, Mann-Whitney t test) in all groups that received an HA stem–binding antibody compared to the control group. Sarah F. Andrews et al. Sci. Immunol. 2017;2:eaan2676 Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works