Antibody neutralizing human respiratory syncytial virus
The present invention relates to monoclonal antibodies which have high anti-RSV neutralizing titers. The invention further provides for isolated nucleic acids encoding the antibodies of the invention and host cells transformed therewith. The invention yet further provides for diagnostic, prophylactic and therapeutic methods employing the antibodies and nucleic acids of the invention, particularly as a passive immunotherapy agent in infants and the elderly.
1. An isolated antibody or antigen binding fragment comprising a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7 and a light chain variable region having the amino acid sequence of SEQ ID NO: 8.
2. The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment thereof binds to human RSV prefusion F protein with a KD value of about 1×10 −9 M to about 1×10 −12 M as determined by surface plasmon resonance.
3. The isolated antibody or antigen binding fragment of claim 1 , which is a full-length antibody having two light chains and two heavy chains, wherein each light chain comprises: a variable region comprising SEQ ID NO: 8 and a human kappa light chain (SEQ ID NO: 14); and each heavy chain comprises: a variable region comprising SEQ ID NO: 7 and a human IgG1 constant region (SEQ ID NO: 13).
4. The isolated antibody of claim 3 , wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 23 and a light chain comprising the amino acid sequence of SEQ ID NO: 25.
5. The isolated antibody of claim 3 , wherein the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO: 23 and the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO: 25.
6. The isolated antibody or antigenic binding fragment of claim 1 which is an IgG antibody.
7. The isolated antibody or antigen binding fragment of claim 1 , which is an antibody, wherein the antibody is produced in a CHO cell.
8. A composition comprising the antibody or antigen binding fragment of claim 1 and a pharmaceutically acceptable carrier or diluent.
9. The composition of claim 8 , further comprising an antibody or an antigen binding fragment thereof against a respiratory pathogen selected from influenza, human cytomegalovirus (hCMV), human metapneumovirus (hMPV), human parainfluenza (hPIV), human rhinovirus (hRV), mycoplasma pneumonia, streptococcus pneumoniae, adenovirus, bocavirus, enterovirus, norovirus or BK virus.
10. The composition of claim 9 , wherein the respiratory pathogen is influenza, hCMV, hMPV, hPIV, norovirus, or BK virus.
11. An immunogenic composition comprising the antibody or antigen binding fragment of claim 1 and an antigen selected from RSV F protein and RSV G protein and fragments thereof.
12. An isolated antibody or antigen binding fragment thereof comprising a light chain immunoglobulin consisting of the amino acid sequence set forth in SEQ ID NO: 25 and a heavy chain immunoglobulin consisting of the amino acid sequence set forth in SEQ ID NO: 23.