Honing a harder-hitting hammerhead improves broadly neutralizing antibody breadth and potency
George K. Lewis
George K. Lewis
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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

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Figure 1

Depiction of the PG9 HCDR3 hammerhead.

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Depiction of the PG9 HCDR3 hammerhead. The Fv region of PG9 is shown wit...
The Fv region of PG9 is shown with the heavy chain in gray and the light chain in cyan. Prominent extension of the hammerhead from the antigen-binding face of the Fv structure is readily apparent at the bottom of the figure. The figure was made with the ICM software suite (Molsoft LLC., La Jolla, California, USA) using PDB: 3u4e from ref. 13.