A Humanized Form of a CD4-Specific Monoclonal Antibody Exhibits Decreased Antigenicity and Prolonged Plasma Half-Life in Rhesus Monkeys While Retaining Its Unique Biological and Antiviral Properties
| Autor: | Wenyu Lin, Beth Browning, Frederick B. Oleson, Sarah A. Bixler, Jodie Lucci, Konrad Miatkowski, Eduardo A. Padlan, Margaret D. Rosa, Thomas H. Parish, Linda C. Burkly, Yen Ming Hsu, Norman L. Letvin, Barbara Ehrenfels, Keith A. Reimann, Dian L. Olson |
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| Rok vydání: | 1997 |
| Předmět: |
CD4-Positive T-Lymphocytes
Antigenicity medicine.drug_class Recombinant Fusion Proteins Molecular Sequence Data Immunology Immunoglobulin Variable Region Simian Acquired Immunodeficiency Syndrome Virus Replication Monoclonal antibody Lymphocyte Depletion Virus Mice Virology medicine Animals Humans Amino Acid Sequence Ibalizumab Base Sequence biology Immunization Passive Antibodies Monoclonal Biological activity Macaca mulatta In vitro Antibodies Anti-Idiotypic Infectious Diseases Viral replication CD4 Antigens HIV-1 biology.protein Antibody medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses. 13:933-943 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.1997.13.933 |
| Popis: | Certain monoclonal antibodies (MAbs) directed against CD4 can efficiently block HIV-1 replication in vitro. To explore CD4-directed passive immunotherapy for prevention or treatment of AIDS virus infection, we previously examined the biological activity of a nondepleting CD4-specific murine MAb, mu5A8. This MAb, specific for domain 2 of CD4, blocks HIV-1 replication at a post-gp120-CD4 binding step. When administered to normal rhesus monkeys, all CD4+ target cells were coated with antibody, yet no cell clearance or measurable immunosuppression occurred. However, strong anti-mouse Ig responses rapidly developed in all monkeys. In the present study, we report a successfully humanized form of mu5A8 (hu5A8) that retains binding to both human and monkey CD4 and anti-AIDS virus activity. When administered intravenously to normal rhesus monkeys, hu5A8 bound to all target CD4+ cells without depletion and showed a significantly longer plasma half-life than mu5A8. Nevertheless, an anti-hu5A8 response directed predominantly against V region determinants did eventually appear within 2 to 4 weeks in most animals. However, when hu5A8 was administered to rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques, anti-hu5A8 antibodies were not detected. Repeated administration of hu5A8 in these animals resulted in sustained plasma levels and CD4+ cell coating with humanized antibody for 6 weeks. These studies demonstrate the feasibility of chronic administration of CD4-specific MAb as a potential means of treating or preventing HIV-1 infection. |
| Databáze: | OpenAIRE |
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