Abstract HIV/AIDS remains one of the most serious threats to global public health. Although anti-HIV drugs have been effective among the wealthiest populations, new methods to prevent infections are needed to control HIV-1 infections globally. Strategies to combat HIV-1 benefit from structural knowledge of how antibodies recognize HIV envelope proteins and how the immune system eliminates viruses. Until recently, only a small number of broadly neutralizing antibodies against HIV-1 had been characterized, and the immunological basis for their breadth and potency remains poorly understood. However, it was recently demonstrated that antibodies could be engineered to greatly enhance their breadth and potency. Unfortunately, these and other engineering efforts can result in a decrease in antibody half-life in various animal models. This decrease in half-life correlates with polyreactivity, an increase in reactivity to a variety of antigens. In order to make better targets for passive delivery therapies, we are using a variety of computational and structure-based techniques. We have constructed several mutations in regions that have been predicted to have high aggregation propensities, and have shown that these novel reagents have reduced polyreactivity and longer in vivo half-lives, yet maintain potency in neutralization assays. Further characterization will help further our understanding of the relationship between antibody potency, polyreactivity, and half-life.

AIDS Research and Human RetrovirusesVol. 30, No. S1 Glycans and Antibody Effector FunctionsEngineering Antibodies to Enhance Activity and Increase Half-lifeStuart A. Sievers, Sonal N. Patel, Kathleen Bennett, Florian Klein, Michel C. Nussenzweig, and Pamela J. BjorkmanStuart A. SieversCalifornia Institute of Technology, Biology and Biological Engineering, Pasadena, CA, United StatesSearch for more papers by this author, Sonal N. PatelCalifornia Institute of Technology, Biology and Biological Engineering, Pasadena, CA, United StatesSearch for more papers by this author, Kathleen BennettCalifornia Institute of Technology, Biology and Biological Engineering, Pasadena, CA, United StatesSearch for more papers by this author, Florian KleinRockefeller University, Laboratory of Molecular Immunology, New York, NY, United StatesSearch for more papers by this author, Michel C. NussenzweigRockefeller University, Laboratory of Molecular Immunology, New York, NY, United StatesSearch for more papers by this author, and Pamela J. BjorkmanCalifornia Institute of Technology, Biology and Biological Engineering, Pasadena, CA, United StatesSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5456.abstractAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Engineering Antibodies to Enhance Activity and Increase Half-life." AIDS Research and Human Retroviruses, 30(S1), p. A210FiguresReferencesRelatedDetailsCited byOvercoming low yields of plant-made antibodies by a protein engineering approach22 December 2015 | Biotechnology Journal, Vol. 11, No. 1Antibody engineering for increased potency, breadth and half-lifeCurrent Opinion in HIV and AIDS, Vol. 10, No. 3 Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Stuart A. Sievers, Sonal N. Patel, Kathleen Bennett, Florian Klein, Michel C. Nussenzweig, and Pamela J. Bjorkman.Engineering Antibodies to Enhance Activity and Increase Half-life.AIDS Research and Human Retroviruses.Oct 2014.A210-A210.http://doi.org/10.1089/aid.2014.5456.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download