Human cytomegalovirus neutralising antibodies and use thereof
The invention relates to neutralizing antibodies and antibody fragments having high potency in neutralizing hCMV, wherein said antibodies and antibody fragments are specific for a combination of hCMV proteins UL130 and UL131A, or for a combination of hCMV proteins UL128, UL130 and UL131A. The invention relates also to immortalized B cells that produce, and to epitopes that bind to, such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies, antibody fragments, and epitopes in screening methods as well as in the diagnosis and therapy of disease.
1. A method of inhibiting human cytomegalovirus (hCMV) infection in a subject, comprising administering an effective amount of an antibody, or antigen binding portion thereof, comprising heavy and light chain variable region CDR1, CDR2, and CDR3 sequences as set forth in SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, respectively, wherein hCMV infection is inhibited.
2. A method of inhibiting hCMV infection in a subject, comprising administering an effective amount of an antibody, or antigen binding portion thereof, comprising heavy and light chain variable regions comprising the amino acid sequence of SEQ ID NO: 63 and SEQ ID NO: 64, respectively, wherein hCMV infection is inhibited.
3. A method of inhibiting hCMV infection in a subject, comprising administering an effective amount of an antibody, or antigen binding portion thereof, that binds to the same epitope as an antibody having heavy and a light chain variable regions comprising the amino acid sequence of SEQ ID NO: 63 and SEQ ID NO: 64, respectively, wherein hCMV infection is inhibited.
4. The method of claim 1 , 2 , or 3 wherein the antibody is a human antibody, a monoclonal antibody, a human monoclonal antibody, a single chain antibody, Fab, Fab′, F(ab′) 2 , Fv or scFv.
5. The method of claim 1 , 2 , or 3 further comprising the administration of a second antibody, or antigen binding fragment thereof, which inhibits hCMV infection.
6. The method of claim 5 , wherein the second antibody, or antigen binding fragment thereof, is specific for the hCMV protein gB.
7. The method of claim 1 , 2 , or 3 wherein the antibody is specific for a complex comprising hCMV proteins UL128, UL130 and UL131A and inhibits infection of endothelial cells, retinal cells, or dendritic cells by hCMV, wherein the concentration of antibody required for 50% inhibition of hCMV is 0.1 μg/ml or less.
8. The method of claim 7 , wherein the concentration of antibody required for 50% inhibition of hCMV is 0.01 μg/ml or less.
9. The method of claim 7 , wherein the concentration of antibody required for 50% inhibition of hCMV is 0.004 μg/ml or less.
10. The method of claim 7 , wherein the antibody binds a conformational epitope formed by the three proteins.