Soluble Human CD4 Elicits an Antibody Response in Rhesus Monkeys that Inhibits Simian Immunodeficiency Virus Replication

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 88; no. 1; pp. 120 - 124
• Main Authors: Watanabe, Mamoru, Chen, Zheng W., Tsubota, Hiroshi, Lord, Carol I., Levine, Cindy G., Letvin, Norman L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01-01-1991; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; AIDS VIRUS; AIDS/HIV; ANIMAL CELLS; ANIMALS; ANTIBODIES; Antibody Formation; BASIC BIOLOGICAL SCIENCES; BIOCHEMISTRY; Blood plasma; Bone marrow; Bone Marrow - immunology; BONE MARROW CELLS; CD4 Antigens - immunology; CELL FLOW SYSTEMS; CHEMISTRY; Colony-Forming Units Assay; CONNECTIVE TISSUE CELLS; Cultured cells; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; GLOBULINS; GLYCOPROTEINS; Humans; Immunization; Immunoglobulin G - analysis; IMMUNOGLOBULINS; IMMUNOLOGY; Lymphocytes - immunology; Macaca mulatta; MACROPHAGES; Macrophages - immunology; MAMMALS; MEMBRANE PROTEINS; MICROORGANISMS; Molecules; MONKEYS; MONOCLONAL ANTIBODIES; ORGANIC COMPOUNDS; PARASITES; PHAGOCYTES; PRIMATES; PROTEINS; RECEPTORS; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - physiology; SOMATIC CELLS; VERTEBRATES; Virus Replication; VIRUSES
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.88.1.120

Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVmac) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). We show that human rsCD4 does not efficiently inhibit SIVmacreplication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIVmacactivity in vitro. Plasma of these animals efficiently blocks SIVmacreplication in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIVmac-infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD44but not CD8+concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals.