Human monoclonal antibody against coreceptors for human immunodeficiency virus
Compositions are provided that comprise antibody against coreceptors for human immunodeficiency virus such as CCR5 and CXCR4. In particular, monoclonal human antibodies against human CCR5 are provided that bind to CCR5 with high affinity and are capable of inhibiting HIV infection at low concentrations. The antibodies can be used as prophylactics or therapeutics to prevent and treat HIV infection, for screening drugs, and for diagnosing diseases or conditions associated with interactions with HIV coreceptors.
1. An isolated antibody that specifically binds to human CCR5, wherein the antibody comprises a heavy chain variable region of SEQ ID NO: 55 and a light chain variable region of SEQ ID NO: 58, a heavy chain variable region of SEQ ID NO: 56 and a light chain variable region of SEQ ID NO: 59, or a heavy chain variable region of SEQ ID NO: 57 and a light chain variable region of SEQ ID NO: 60.
2. The antibody of claim 1 , wherein the antibody specifically binds to loop 6 of human CCR5 and inhibits infection of immunodeficiency virus of human cells.
3. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
4. The antibody of claim 3 , wherein the monoclonal antibody is a single chain antibody.
5. The antibody of claim 4 , wherein the single chain antibody comprises an amino acid sequence selected from SEQ ID Nos: 27, 29, and 31.
6. The antibody of claim 4 , wherein the antibody has an amino acid sequence of SEQ ID NO: 27.
7. The antibody of claim 4 , wherein the antibody is encoded by a polynucleotide selected from the group consisting of SEQ ID NOs: 26, 28, and 30.
8. The antibody of claim 1 , wherein the antibody specifically binds to loop 6 of human CCR5 which comprises SEQ ID NO: 2.
9. A recombinant expression vector encoding a polypeptide selected from the group consisting of SEQ ID NOs: 36-41.
10. The recombinant expression vector of claim 9 is a bacterial, yeast, plant, mammalian or viral expression vector.
11. A recombinant cell expressing a polypeptide selected from the group consisting of SEQ ID NOs: 36-41.
12. The recombinant cell of claim 11 is a bacterial, yeast, plant or mammalian cell.
13. The recombinant cell of claim 11 is a human cell.