Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency
George K. Lewis
George K. Lewis
Published May 18, 2015
Citation Information: J Clin Invest. 2015;125(6):2271-2274. https://doi.org/10.1172/JCI82057.
View: Text | PDF
Commentary

Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency

Abstract

While current HIV-1 therapies have greatly improved the quality and duration of life for infected individuals, a vaccine to prevent transmission of the virus is lacking. Broadly neutralizing monoclonal antibodies (bnmAbs) with the capacity to neutralize multiple HIV-1 variants have been isolated from HIV-1–infected individuals, and there has been a great effort to investigate how these bnmAbs arise, due their potential for HIV-1 vaccination. In this issue of the JCI, Willis and colleagues apply a computational approach to design variants of the bnmAb PG9 in an attempt to enhance potency and neutralization breadth. One of these variants was able to target multiple PG9-resistant strains, as the result of stabilization of the long heavy chain complementarity determining region 3 (HCDR3). The results of this study provide important insight and a unique approach to optimizing HIV-1 bnmABs.

Authors

George K. Lewis

×

Figure 2

Hammerhead binding to the PG9 epitope.

Options: View larger image (or click on image) Download as PowerPoint
Hammerhead binding to the PG9 epitope. The hammerhead is shown as a gray...
The hammerhead is shown as a gray ribbon with N100F shown as ball and sticks. The glycan at N160 is shown as a yellow surface, the glycan at N156 is shown as a green surface, and V1/V2 is shown as a red surface. HCDR3 contacts all three structures where the most prominent are with the glycan at N160 (further details in ref. 13). The carboxamide side chain of N100F does not contact any of the epitope residues. The figure was generated as in Figure 1 using PDB:3u4e (13) and PDB:4tvp (10).