title: Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice.
abstract: 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.
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA. Electronic address: cheryl.stoddart@ucsf.edu.
authors: Cheryl A
authors: CA
authors: Stoddart
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Sofiya A
authors: SA
authors: Galkina
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Pheroze
authors: P
authors: Joshi
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Galina
authors: G
authors: Kosikova
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Brian R
authors: BR
authors: Long
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Ekaterina
authors: E
authors: Maidji
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Mary E
authors: ME
authors: Moreno
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Jose M
authors: JM
authors: Rivera
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Ukina R
authors: UR
authors: Sanford
authors: Division of Experimental Medicine, Department of Medicine, San Francisco General Hospital, University of California, Box 1234, San Francisco, San Francisco, CA 94143, USA.
authors: Barbara
authors: B
authors: Sloan
authors: Theraclone Sciences, Inc., Seattle, WA 98104, USA.
authors: Witold
authors: W
authors: Cieplak
authors: Monogram Biosciences, South San Francisco, CA 94080, USA.
authors: Terri
authors: T
authors: Wrin
authors: Theraclone Sciences, Inc., Seattle, WA 98104, USA.
authors: Po-Ying
authors: PY
authors: Chan-Hui
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000627:therapeutic use*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV infection; HIV pathogenesis; Humanized mouse; Neutralizing antibody; Passive immunization