Antibody-based inhibitors of HIV infection

Abstract

The demand for new treatment options against HIV is becoming increasingly desperate as the side effects and the expansion and spread of drug-resistant virus within the infected population limit the clinical benefits provided by available anti-HIV drugs. Preparations of polyclonal antibodies have a long history of proven clinical utility against some viruses; however, they have enjoyed very limited success against HIV. Recent clinical trials and in vitro experiments suggest that monoclonal antibodies against HIV may have promise clinically. These antibodies and antibody-based reagents target either the viral envelope glycoprotein, the receptor (CD4) or coreceptor (CCR5) molecules, or transition-state structures that appear during viral entry. The challenge is whether an antibody-based therapy can be identified (with or without their small molecule brethren) that presents long-term clinical efficacy, low toxicity and minimal risk of clinical failure from viral resistance.

Keywords::

• antibody therapeutics
• envelope glycoprotein
• fusion
• HIV
• neutralisation
• vaccine

Acknowledgements

The authors thank R Blumenthal, P Kwong and H Golding for helpful discussions. This project was supported by the NIH Intramural AIDS Targeted Antiviral Program (IATAP), the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the Gates Foundation to DSD, DHHS NO1-CO-12400 to MYZ, and CRADA between NCI and Profectus BioSciences, Inc.