HIV Neutralization by Structure-Based Enhancements of CD4-Molecular Mimicry
Description of Invention:
Available for licensing are compositions and methods for inhibiting CD4 - gp120 interactions. HIV infectivity is mediated by interactions between the lymphocyte cellular protein CD4 and HIV exterior gp120 envelope glycoprotein. The invention presents crystal structures of a number of co-complexes between CD4 mimics, CD4M33, F23, and others disclosed herein, with gp120, as well as other mimics and molecules, which interact with gp120. CD4M33 has greater affinity than F23 for HIV-1 primary isolates, whereas F23 is a better mimic of CD4 and showed greater neutralization breadth than CD4M33 against diverse isolates from HIV-1, HIV-2, and SIVcpz. These results provide a basis for the development of anti-HIV antagonists with increased breadth of neutralization. Moreover, methods are disclosed for the identification of a mimic of CD4 with possible broad-spectrum activity. These methods can be used for drug screening and variant CD4 mimic production. Also, methods are provided for characterizing and evaluating protein structure, for designing candidate ligands, and for constructing CD4 mimetic antagonist or the interfacial cavity binding compounds.
Finally, provided are methods for producing mono- and polyclonal antibodies for use in vaccines. Mimics binding to gp120 cause conformational change in the protein, thus exposing epitope regions for antibody recognition. The uses of the mimetics and also of a mimetic-based immunogen in inhibiting, reducing, or preventing HIV infection are also discussed. Suggestions are presented for therapeutic uses of the antibodies in preventing a decline in CD4 T cell levels in HIV-positive patients.
Inventors:
Peter D. Kwong (NIAID) Chih-chin Huang (NIAID) Tongqing Zhou (NIAID) et al.
Patent Status:
DHHS Reference No. E-333-2004/0 Licensing Status: This technology is no longer available for licensing.
For Additional Information Please Contact: Michael Shmilovich J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5019
Email: shmilovm@mail.nih.gov
Fax: (301) 402-0220
