Broadly Neutralizing Monoclonal Antibodies Against HIV-1 V1V2 Env Region

Abstract

The present invention relates anti-HIV therapies and prophylaxis. Specifically, the invention relates to broadly neutralizing antibodies against HIV-1, nucleic acids encoding these antibodies, vectors comprising the nucleic acids and cells and pharmaceutical compositions Comprising said vectors and/or antibodies. The present invention also relates to use of the antibodies and/or vectors for the treatment and/or prevention of HIV-1 infection in a subject. Furthermore, the invention also relates to a kit containing the antibodies of the invention.

1 .- 15 . (canceled) 
     
     
         16 . An isolated anti-HIV-1 antibody which binds to V1V2, wherein the antibody comprises:
 (i) a variable heavy chain sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:172; and   (ii) a variable light chain sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:173.   
     
     
         17 . The isolated anti-HIV-1 antibody of  claim 16 , wherein the antibody comprises:
 (i) a variable heavy chain sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:172; and   (ii) a variable light chain sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:173.   
     
     
         18 . The isolated anti-HIV-1 antibody of  claim 16 , wherein the antibody comprises:
 a variable heavy chain sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:172; and   (ii) a variable light chain sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO:173.   
     
     
         19 . The isolated anti-HIV-1 antibody of  claim 16 , wherein the heavy chain sequence comprises a CDR1 comprising the amino acids at positions 31-35 of SEQ ID NO:172, a CDR2 comprising the amino acids at positions 50-66 of SEQ ID NO:172, and a CDR3 comprising the amino acids at positions 99-134 of SEQ ID NO:172. 
     
     
         20 . The isolated anti-HIV-1 antibody of  claim 16 , wherein the light chain sequence comprises a CDR1 comprising the amino acids at positions 23-35 of SEQ ID NO:173, a CDR2 comprising the amino acids at positions 51-57 of SEQ ID NO:173, and a CDR3 comprising the amino acids at positions 90-101 of SEQ ID NO:173. 
     
     
         21 . An isolated anti-HIV-1 antibody of  claim 16 , wherein the antibody neutralizes autologous HIV-1 virus CAP256.SU at an IC 50  concentration of less than 0.5 μ/ml, or heterologous HIV-1 virus ZM53.12 at an IC 50  concentration of less than 0.5 μg/ml. 
     
     
         22 . An isolated anti-HIV-1 antibody of  claim 18 , wherein the antibody neutralizes autologous HIV-1 virus CAP256.SU at an IC 50  concentration of less than 0.5 μ/ml, or heterologous HIV-1 virus ZM53.12 at an IC 50  concentration of less than 0.5 μg/ml. 
     
     
         23 . An isolated anti-HIV-1 antibody of  claim 20 , wherein the antibody neutralizes autologous HIV-1 virus CAP256.SU at an IC 50  concentration of less than 0.5 μ/ml, or heterologous HIV-1 virus ZM53.12 at an IC 50  concentration of less than 0.5 μg/ml. 
     
     
         24 . An isolated anti-HIV-1 antibody of  claim 16 , wherein the antibody is a Fab, Fab′, a F(ab)′2, a single-chain Fv (scFv), an Fv fragment, or a linear antibody. 
     
     
         25 . An isolated anti-HIV-1 antibody of  claim 18 , wherein the antibody is a Fab, Fab′, a F(ab)′2, a single-chain Fv (scFv), an Fv fragment, or a linear antibody. 
     
     
         26 . An isolated anti-HIV-1 antibody of  claim 20 , wherein the antibody is a Fab, Fab′, a F(ab)′2, a single-chain Fv (scFv), an Fv fragment, or a linear antibody. 
     
     
         27 . A composition comprising the isolated anti-HIV-1 antibody of  claim 16 , or a fragment thereof. 
     
     
         28 . A composition comprising the isolated anti-HIV-1 antibody of  claim 18 , or a fragment thereof. 
     
     
         29 . A composition comprising the isolated anti-HIV-1 antibody of  claim 20 , or a fragment thereof. 
     
     
         30 . A pharmaceutical composition comprising an isolated anti-HIV-1 antibody of  claim 16 , or a fragment thereof, and a pharmaceutically acceptable carrier. 
     
     
         31 . A pharmaceutical composition comprising an isolated anti-HIV-1 antibody of  claim 18 , or a fragment thereof, and a pharmaceutically acceptable carrier. 
     
     
         32 . A pharmaceutical composition comprising an isolated anti-HIV-1 antibody of  claim 20 , or a fragment thereof, and a pharmaceutically acceptable carrier. 
     
     
         33 . A method of inhibiting HIV-1 replication or reducing HIV-1 viral load in a subject, the method comprising administering an isolated anti-HIV-1 antibody of  claim 16 , or a fragment thereof, to the subject. 
     
     
         34 . A method of inhibiting HIV-1 replication or reducing HIV-1 viral load in a subject, the method comprising administering an isolated anti-HIV-1 antibody of  claim 18 , or a fragment thereof, to the subject. 
     
     
         35 . A method of inhibiting HIV-1 replication or reducing HIV-1 viral load in a subject, the method comprising administering an isolated anti-HIV-1 antibody of  claim 20 , or a fragment thereof, to the subject. 
     
     
         36 . The method of  claim 33 , further comprising the administration of a second therapeutic agent. 
     
     
         37 . The method of  claim 34 , further comprising the administration of a second therapeutic agent. 
     
     
         38 . The method of  claim 35 , further comprising the administration of a second therapeutic agent. 
     
     
         39 . The method of  claim 36 , wherein said second therapeutic agent is an antiviral agent. 
     
     
         40 . The method of  claim 37 , wherein said second therapeutic agent is an antiviral agent. 
     
     
         41 . The method of  claim 38 , wherein said second therapeutic agent is an antiviral agent. 
     
     
         42 . A kit comprising a container containing an isolated anti-HIV-1 antibody of  claim 16 , or fragment thereof. 
     
     
         43 . A kit comprising a container containing an isolated anti-HIV-1 antibody of  claim 18 , or fragment thereof. 
     
     
         44 . A kit comprising a container containing an isolated anti-HIV-1 antibody of  claim 20 , or fragment thereof.