title: CD4-immunoglobulin G2 protects Hu-PBL-SCID mice against challenge by primary human immunodeficiency virus type 1 isolates.
abstract: CD4-immunoglobulin G2 (IgG2) is a fusion protein comprising human IgG2 in which the Fv portions of both heavy and light chains have been replaced by the V1 and V2 domains of human CD4. Previous studies found that CD4-IgG2 potently neutralizes a broad range of primary human immunodeficiency virus type 1 (HIV-1) isolates in vitro and ex vivo. The current report demonstrates that CD4-IgG2 protects against infection by primary isolates of HIV-1 in vivo, using the hu-PBL-SCID mouse model. Passive administration of 10 mg of CD4-IgG2 per kg of body weight protected all animals against subsequent challenge with 10 mouse infectious doses of the laboratory-adapted T-cell-tropic isolate HIV-1(LAI), while 50 mg of CD4-IgG2 per kg protected four of five mice against the primary isolates HIV-1(JR-CSF) and HIV-1(AD6). In contrast, a polyclonal HIV-1 Ig fraction exhibited partial protection against HIV-1(LAI) at 150 mg/kg but no significant protection against the primary HIV-1 isolates. The results demonstrate that CD4-IgG2 effectively neutralizes primary HIV-1 isolates in vivo and can prevent the initiation of infection by these viruses.
authors.affiliation: The Aaron Diamond AIDS Research Center and The Rockefeller University, New York, New York 10016, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Gauduin
authors.forename: G P
authors.initials: GP
authors.lastname: Allaway
authors.forename: W C
authors.initials: WC
authors.lastname: Olson
authors.forename: R
authors.initials: R
authors.lastname: Weir
authors.forename: P J
authors.initials: PJ
authors.lastname: Maddon
authors.forename: R A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D016860:CD4 Immunoadhesins / Q000008:administration & dosage / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D016513:Mice, SCID
chemical_list: D019380:Anti-HIV Agents; D016860:CD4 Immunoadhesins; C096753:CD4-IgG(2); D015483:HIV Antibodies; D007074:Immunoglobulin G