Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice
| Autor: | Witold Cieplak, Brian Long, Terri Wrin, Barbara Sloan, Jose M. Rivera, Sofiya A. Galkina, Ukina R. Sanford, Mary E. Moreno, Po-Ying Chan-Hui, Pheroze Joshi, Ekaterina Maidji, Cheryl A. Stoddart, Galina Kosikova |
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| Rok vydání: | 2014 |
| Předmět: |
Male
HIV Infections Mice SCID HIV Antibodies HIV Envelope Protein gp120 Medical and Health Sciences Epitope Mice Monoclonal Neutralizing antibody Neutralizing Antibodies Monoclonal virus diseases Biological Sciences Human Fetal Tissue Infectious Diseases Treatment Outcome HIV pathogenesis HIV/AIDS Antibody Infection Biotechnology medicine.drug_class Humanized mouse Biology SCID Monoclonal antibody Antibodies Article Virus Virology medicine Animals Agricultural and Veterinary Sciences Animal Inoculation Prevention Passive immunization HIV infection Antibodies Neutralizing In vitro Disease Models Animal Good Health and Well Being Disease Models Immunology HIV-1 biology.protein Immunization |
| Zdroj: | Virology, vol 462-463, iss 1 |
| ISSN: | 0042-6822 |
| Popis: | Highly potent broadly neutralizing human monoclonal antibodies hold promise for HIV prophylaxis and treatment. We used the SCID-hu Thy/Liv and BLT humanized mouse models to study the efficacy of these antibodies, primarily PG16, against HIV-1 clades A, B, and C. PG16 targets a conserved epitope in the V1/V2 region of gp120 common to 70–80% of HIV-1 isolates from multiple clades and has extremely potent in vitro activity against HIVJR-CSF. PG16 was highly efficacious in SCID-hu mice as a single intraperitoneal administration the day before inoculation of R5-tropic HIV directly into their Thy/Liv implants and demonstrated even greater efficacy if PG16 administration was continued after Thy/Liv implant HIV inoculation. However, PG16 as monotherapy had no activity in humanized mice with established R5-tropic HIV infection. These results provide evidence of tissue penetration of the antibodies, which could aid in their ability to prevent infection if virus crosses the mucosal barrier. |
| Databáze: | OpenAIRE |
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