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Prevention of HIV-1 IIIB infection in chimpanzees by CD4 immunoadhesin

Naturevolume 352pages434436 (1991) | Download Citation

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Abstract

THE first step in infection by the human immunodeficiency virus (HIV) is the specific binding of gp!20, the envelope glycoprotein of HIV, to its cellular receptor, CD4 (see ref. 1 for review). To inhibit this interaction, soluble CD4 analogues that compete for gp120 binding and block HIV infection in vitro have been developed2–8. To determine whether these analogues can protect an uninfected individual from challenge with HIV, we used the chimpanzee model system of cell-free HIV infection. Chimpanzees are readily infected with the IIIB strain of HIV-1, becoming viraemic within about 4–6 weeks of challenge, although they do not develop the profound CD4+ T-cell depletion and immunodeficiency characteristic of HIV infection in humans9. CD4 immunoadhesin (CD4–IgG), a chimaeric molecule consisting of the N-terminal two immunoglobulin-like regions of CD4 joined to the Fc region of human IgG1 (refs 8, 10), was selected as the CD4 analogue for testing because it has a longer half-life than CD4, contributed by the IgG Fc portion of the molecule. In humans, this difference results in a 25-fold increased concentration of CD4–IgG in the blood compared with recombinant CD4 (ref. 11). Here we report that pretreatment with CD4–IgG can prevent the infection of chimpanzees with HIV-1. The need for a preventative agent is particularly acute in perinatal HIV transmission. As recombinant CD4–IgG, like the parent IgG molecule, efficiently crosses the primate placenta10, it may be possible to set up an immune state in a fetus before HIV transfer occurs, thus preventing infection.

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Author information

Author notes

    • Jorg W. Eichberg

    Present address: Wyeth-Ayerst Research, 145 King of Prussia Road, Philadelphia, Pennsylvania, 19087, USA

  1. Daniel J. Capon: Cell Genesys Inc., 344 Lakeside Drive, Foster City, California 94404, USA

  2. Catherine M. Jett, Krishna K. Murthy and Jorg W. Eichberg: Southwest Foundation for Biomedical Research, San Antonio, Texas 78284, USA

  3. Alfred M. Prince: The Lindsley F. Kimball Research Institute of the NY Blood Center, 310 East 67th Street, New York 10021, USA

Affiliations

  1. Genentech Inc., 460 Pt San Bruno Boulevard, S. San Francisco, California, 94080, USA

    • Rebecca H. R. Ward
    • , Daniel J. Capon
    • , Catherine M. Jett
    • , Krishna K. Murthy
    • , Joyce Mordenti
    • , Catherine Lucas
    • , Steve W. Frie
    • , Alfred M. Prince
    • , James D. Green
    •  & Jorg W. Eichberg

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https://doi.org/10.1038/352434a0

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