Research press release


Nature Biotechnology

Playing offense to HIV’s defense



David Hoたちはこの隙間がHIV-1の抵抗性に寄与していると考え、これを「埋めて」やれば、ウイルスの抗体回避作戦に対抗できるのではないかと推論した。この理論を検証するために、Hoたちはイバリズマブのウイルス結合部位の周辺に糖鎖を付加した。この糖鎖付加した抗体は、付加していない抗体に対して抵抗性を示すHIV-1系統も含め、調べたHIV-1系統全てを中和した。

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.

doi: 10.1038/nbt.2677


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