Playing offense to HIV’s defense

An approach which resurrects the potency of therapeutic antibodies against which HIV has developed resistance is reported in a paper published in Nature Biotechnology this week. In addition to describing a method to engineer an antibody that appears effective against a large number of HIV-1 strains, the authors suggest that the engineering strategy presented might be useful for improving other therapeutic antibodies.

The antibody described in the study, ibalizumab, acts by blocking a receptor that HIV-1 uses to enter cells. However, HIV-1 strains in some patients treated with ibalizumab acquire particular mutations that make them resistant to the antibody. Structural studies have showed that these mutations loosen the interaction between HIV-1 and ibalizumab by introducing a gap between the virus and the antibody.

Suspecting that this gap contributes to HIV-1 resistance, David Ho and colleagues reasoned that ‘refilling’ it would counter the virus’ evasive maneuver. To test this theory they tagged ibalizumab with a carbohydrate near its site of interaction with the virus. The carbohydrate-tagged antibody neutralized 100% of tested HIV-1 strains, including strains resistant to the unmodified antibody.