Novel Broadly Cross-Reactive HIV Neutralizing Human Monoclonal Antibodies Selected from Fab Phage Display Libraries Using a Novel Strategy Based on Alternative Antigen Panning
and
Novel Broadly Cross-Reactive HIV-1 Neutralizing Human Single-Chain Antibodies Derived from X5 by DNA Shuffling and Alternating Antigen Panning
Description of Invention:
This invention (E-144-02/0) identifies four antibodies, designed m12, m14, m16, and m18. These four antibodies were isolated from a human Fab phage display library using alternating antigen panning (AAP). All four antibodies bind to recombinant HIV envelope glycoproteins (Env) gp12089.6, gp120JR-FL and gp120IIIB with high affinity. Moreover, m12 binding to gp 120 or gp 140 is significantly enhanced in the presence of the receptor CD4. The second invention (E-144-02/1) describes two scFv clones, designated M6 and M9 that were selected from phage-displayed X5 scFv mutants library by panning the library against gp12089.6/IIIB-CD4 complex using the same strategy, alternating antigen panning strategy (AAP). M6 and M9 are more stable than previously reported HIV-1 antibody named X5 and have significant improved binding activities to gp120IIIB. Both scFvs inhibit more efficiently membrane fusion mediated by envelope glycoproteins of primary HIV isolates with a broader spectrum compared to X5, indicating that scFv format may be a more proper format compared to Fab for HIV-1 neutralizing antibodies to inhibit virus infection and transmission. Furthermore, scFv is a single molecule with almost half size of Fab, which makes scFv more suitable for constructing bivalent and multivalent antibodies and antibody fusion proteins. Thus, since all six antibodies from the above two inventions cross-react with different HIV-1 isolates, these antibodies could be directly used for therapy of HIV-1 infected individuals. In addition, these antibodies can be also used for screening of peptide phage display libraries, libraries of Envs, and in general as tools for development of HIV vaccines.
Inventors:
Dimiter S. Dimitrov (NCI) and Mei-Yun Zhang (SAIC)
Patent Status:
DHHS Reference No. E-144-02/0 filed 05 May 2002
DHHS Reference No. E-144-02/1 filed 05 May 2002
For Additional Information Please Contact: Sally Hu PhD MBA
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5606
Email: hus@mail.nih.gov
Fax: (301) 402-0220
