Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.
Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.
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DOI：
10.1038/ncomms9443
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发表时间：
2015-09-29
影响因子：
16.6
通讯作者：
Lee B
中科院分区：
文献类型：
--
作者：
Webb NE;Montefiori DC;Lee B
A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose–response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120–gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations. Potencies of HIV broadly neutralizing antibodies are usually defined by their in vitro IC50 and IC80 values, but much higher levels will be required for successful immunotherapies. Here, Webb et al. predict antibody potency at therapeutic levels by analyzing dose–response curve slopes, which correlate with epitope class.
