Engineered Bispecific Antibodies with Exquisite HIV-1-Neutralizing Activity.

Abstract

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, 10E8V2.0/iMab, neutralized 118 HIV-1 pseudotyped viruses tested with a mean 50% inhibitory concentration (IC50) of 0.002 μg/mL. 10E8V2.0/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 ∼50% of new infections worldwide. Importantly, 10E8V2.0/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.

• Authors: Yaoxing Huang, Jian Yu, Anastasia Lanzi, Xin Yao, Chasity D Andrews, Lily Tsai, Mili R Gajjar, Ming Sun, Michael S Seaman, Neal N Padte, David D Ho
• Journal: Cell (Cell) Vol. 165 Issue 7 Pg. 1621-1631 (Jun 16 2016) ISSN: 1097-4172 [Electronic] United States
• PMID: 27315479 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal
• Antibodies, Neutralizing
• HIV Envelope Protein gp160

Topics

• Animals
• Antibodies, Bispecific (chemistry, immunology)
• Antibodies, Monoclonal (chemistry)
• Antibodies, Neutralizing (chemistry, immunology)
• HIV Envelope Protein gp160 (chemistry, immunology)
• HIV Infections (prevention & control, therapy)
• HIV-1 (immunology)
• Humans
• Immunization, Passive
• Mice