Rapid elicitation of broadly neutralizing antibodies to HIV Env
The present disclosure relates to methods for generating broadly neutralizing bovine anti-HIV Env antibodies, compositions comprising the broadly neutralizing bovine antibodies, and methods of treatment or prevention of HIV using the broadly neutralizing bovine antibodies. In certain embodiments, a broadly neutralizing bovine antibody comprises a polyclonal F(ab) or F(ab′)2 fragment. In certain embodiments, a broadly neutralizing bovine antibody comprises a humanized bovine monoclonal antibody.
1. An isolated monoclonal antibody that specifically binds to HIV Env and comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, and wherein the VH CDR1, VH CDR2, VL CDR1, VL CDR2, and VL CDR3 are from
a) NC-Cow1, NC-Cow7, NC-Cow8, NC-Cow9, or NC-Cow10; or
b) germline reverted NC-Cow1.
2. An isolated monoclonal antibody that specifically binds to HIV Env and comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequence of SEQ ID NO: 1, 2, 3, 4, 5 and 6, respectively.
3. The isolated monoclonal antibody of claim 2 , wherein the antibody is a recombinant antibody, a chimeric antibody, a humanized antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody.
4. The isolated monoclonal antibody of claim 2 , wherein the heavy chain variable region (VH) comprises an amino acid sequence that is at least about 90% identical to SEQ ID NO: 7 and
wherein the light chain variable region (VL) comprises an amino acid sequence that is at least about 90% identical to SEQ ID NO: 8.
5. The monoclonal antibody of claim 2 , wherein the antibody is capable of neutralizing at least two cross-clade isolates of HIV.
6. A pharmaceutical composition comprising the monoclonal antibody of claim 2 and a pharmaceutically acceptable excipient.
7. An isolated polynucleotide encoding the monoclonal antibody of claim 2 .
8. A recombinant virus comprising the polynucleotide of claim 7 .
9. A method of producing an antibody that binds to HIV comprising culturing a host cell comprising the polynucleotide of claim 7 so that the polynucleotide is expressed and the antibody is produced.
10. A method of neutralizing an HIV virus comprising contacting the virus with a sufficient amount of the monoclonal antibody of claim 2 .
11. A method for passively immunizing a subject comprising administering to the subject in need thereof an effective amount of the monoclonal antibody of claim 2 .
12. A method of treating HIV/AIDS comprising administering to a subject in need thereof a therapeutically sufficient amount of the monoclonal antibody of claim 2 .
13. The method of claim 12 , further comprising administering at least one additional therapeutic agent.