Chimeric proteins for prevention and treatment of hiv infection

A nucleic acid molecule, herein designated 632-3, having binding specificity for at least two different sites, at least one site being on the HIV envelope glycoprotein gp120 and the other site being either on said gp120 protein or on the extracellular portion of human CD4, wherein the binding to said at least one site on said gp120 protein is independent of its binding to said other site on said gp120 protein on said extracellular portion of human CD4, said chimeric protein essentially comprising:

• (a) a first binding region comprising the two extracellular membrane distal domains of CD4, V1 and V2, encoded by the DNA sequence substantially as denoted by SEQ ID NO:
• 24;
• (b) a second binding region comprising a binding site derived from a variable region of an antibody heavy chain encoded by the VH3-23 gene, substantially as denoted by SEQ ID NO:
• 25;
• (c) a linker comprising the amino acid sequence substantially as denoted by SEQ ID NO:
• 17, and encoded by the nucleic acid sequence substantially as denoted by SEQ ID NO:
• 18;
• and
• (d) a portion of a constant region of an immunoglobulin chain encoded by the DNA sequence substantially as denoted by SEQ ID NO:
• 26.

A chimeric protein having binding specificity for at least two different sites, at least one site being on the HIV envelope glycoprotein gp120 and the other site being either on said gp120 protein or on the extracellular portion of human CD4, wherein the binding of said chimeric protein to said at least one site on said gp120 protein is independent of its binding to said other site on said gp120 protein or on said extracellular portion of human CD4, said chimeric protein essentially comprising:

• (a) a first binding region comprising a soluble extracellular portion of human CD4;
• (b) a second binding region comprising a variable region of an antibody heavy chain, that is capable of being attached to an adjacent and non-overlapping site on the said gp120 protein or to a site on said extracellular portion of human CD4, and is capable of increasing the capacity of the said extracellular portion of human CD4 to interact with gp120 and to block the interaction of HIV with membranal CD4;
• and
• (c) a linker region that physically connects both binding regions (a) and (b).

A chimeric protein having binding specificity for at least two different sites, at least one site being on the HIV envelope glycoprotein gp120 and the other site being either on said gp120 protein or on the extracellular portion of human CD4, wherein the binding to said at least one site on said gp120 protein is independent of its binding to said other site on said gp120 protein or on said extracellular portion of human CD4, said chimeric protein essentially comprising:

• (a) a first binding region comprising the two extracellular membrane distal domains of CD4, V1 and V2, encoded by the DNA sequence substantially as denoted by SEQ ID NO:
• 24;
• (b) a second binding region comprising a binding site derived from a variable region of an antibody heavy chain encoded by the VH3-23 gene, substantially as denoted by SEQ ID NO:
• 25;
• (c) a linker comprising the amino acid sequence substantially as denoted by SEQ ID NO:
• 17, and encoded by the nucleic acid sequence substantially as denoted by SEQ ID NO:18;
• and
• (d) a portion of a constant region of an immunoglobulin chain encoded by the DNA sequence substantially as denoted by SEQ ID NO:
• 26.