4.8 Article

Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity

期刊

CELL
卷 165, 期 7, 页码 1621-1631

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CELL PRESS
DOI: 10.1016/j.cell.2016.05.024

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  1. Bill and Melinda Gates Foundation [OPP50714, OPP1040732, 1032144]
  2. National Institutes of Health [DP1DA033263]

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While the search for an efficacious HIV-1 vaccine remains elusive, emergence of a new generation of virus-neutralizing monoclonal antibodies (mAbs) has re-ignited the field of passive immunization for HIV-1 prevention. However, the plasticity of HIV-1 demands additional improvements to these mAbs to better ensure their clinical utility. Here, we report engineered bispecific antibodies that are the most potent and broad HIV-neutralizing antibodies to date. One bispecific antibody, 10E8(V2.0)/iMab, neutralized 118 HIV-1 pseudotyped viruses tested with a mean 50% inhibitory concentration (IC50) of 0.002 mu g/mL. 10E8(V2.0)/iMab also potently neutralized 99% of viruses in a second panel of 200 HIV-1 isolates belonging to clade C, the dominant subtype accounting for similar to 50% of new infections worldwide. Importantly, 10E8(V2.0)/iMab reduced virus load substantially in HIV-1-infected humanized mice and also provided complete protection when administered prior to virus challenge. These bispecific antibodies hold promise as novel prophylactic and/or therapeutic agents in the fight against HIV-1.

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