Expression and characterization of human CD4:immunoglobulin fusion proteins.
Different chimeric antibody-like molecules consisting of the four human CD4 extracellular domains (amino acids 1-369) fused to different parts of human IgG1 and IgM heavy-chain constant regions have been created and expressed in mammalian cells. For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region. The chimeric molecules are potent inhibitors of human immunodeficiency virus (HIV) infection and HIV-mediated cytotoxicity. A CD4:IgG1 hinge fusion protein, which was analyzed in more detail, binds efficiently to HIV gp160 and human Fc receptors and shows complement-assisted inhibition of viral propagation in culture. Half-life studies after intravenous application of the latter human fusion protein into mice and monkeys showed significant prolongation of serum survival compared to soluble CD4. An IgG2b murine homolog of the human CD4:IgG1 hinge fusion protein was prepared and evaluated in mice, where it was found to be nontoxic and to have no detectable effect on the humoral response to soluble antigen.
Research Laboratories of Behringwerke AG, Marburg, West Germany.
G
G
Zettlmeissl
J P
JP
Gregersen
J M
JM
Duport
S
S
Mehdi
G
G
Reiner
B
B
Seed
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005260:Female; D015686:Gene Products, env / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects; D006678:HIV / Q000187:drug effects*; D019302:HIV Envelope Protein gp160; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D015704:CD4 Antigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins