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Cell. 2016 Jun 16;165(7):1621-1631. doi: 10.1016/j.cell.2016.05.024.

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

Author information

1
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
2
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
3
Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Electronic address: dho@adarc.org.

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.

PMID:
27315479
PMCID:
PMC4972332
DOI:
10.1016/j.cell.2016.05.024
[Indexed for MEDLINE]
Free PMC Article

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