Anti-HIV antibodies
Provided herein are anti-HIV Env antibodies and their use in the treatment or prevention of HIV/AIDS.
1 . A method of neutralizing a human immunodeficiency virus (HIV) comprising contacting the virus with a sufficient amount of an isolated monoclonal antibody that specifically binds to HIV envelope glycoprotein (Env) and comprises a heavy chain variable region (VH) comprising a VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 and a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3, wherein
(a) the VH CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 1-18;
(b) the VH CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 19-36;
(c) the VH CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 37-54;
(d) the VL CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 55-72;
(e) the VL CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 73-90; and
(f) the VL CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 91-108.
2 . A method for passively immunizing a subject comprising administering to the subject in need thereof an effective amount of a monoclonal antibody or an isolated polynucleotide encoding the antibody, wherein the antibody specifically binds to human immunodeficiency virus envelope glycoprotein (HIV Env) and comprises a heavy chain variable region (VH) comprising a VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 and a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3, wherein
(a) the VH CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 1-18;
(b) the VH CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 19-36;
(c) the VH CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 37-54;
(d) the VL CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 55-72;
(e) the VL CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 73-90; and
(f) the VL CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 91-108.
3 . A method of treating human immunodeficiency virus/acquired immunodeficiency syndrome comprising administering to a subject in need thereof a therapeutically sufficient amount of a monoclonal antibody or an isolated polynucleotide encoding the antibody, wherein the antibody specifically binds to human immunodeficiency virus envelope glycoprotein (HIV Env) and comprises a heavy chain variable region (VH) comprising a VH complementarity determining region 1 (CDR1), VH CDR2, and VH CDR3 and a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3, wherein
(a) the VH CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 1-18;
(b) the VH CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 19-36;
(c) the VH CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 37-54;
(d) the VL CDR1 comprises any one of the amino acid sequences of SEQ ID NOs: 55-72;
(e) the VL CDR2 comprises any one of the amino acid sequences of SEQ ID NOs: 73-90; and
(f) the VL CDR3 comprises any one of the amino acid sequences of SEQ ID NOs: 91-108.
4 . The method of claim 3 , further comprising administering at least one additional therapeutic agent.
5 . The method of claim 2 , wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of
(a) SEQ ID NOs: 1, 19, 37, 55, 73, and 91, respectively;
(b) SEQ ID NOs: 2, 20, 38, 56, 74, and 92, respectively;
(c) SEQ ID NOs: 3, 21, 39, 57, 75, and 93, respectively;
(d) SEQ ID NOs: 4, 22, 40, 58, 76, and 94, respectively;
(e) SEQ ID NOs: 5, 23, 41, 59, 77, and 95, respectively;
(f) SEQ ID NOs: 6, 24, 42, 60, 78, and 96, respectively;
(g) SEQ ID NOs: 7, 25, 43, 61, 79, and 97, respectively;
(h) SEQ ID NOs: 8, 26, 44, 62, 80, and 98, respectively;
(i) SEQ ID NOs: 9, 27, 45, 63, 81, and 99, respectively;
(j) SEQ ID NOs: 10, 28, 46, 64, 82, and 100, respectively;
(k) SEQ ID NOs: 11, 29, 47, 65, 83, and 101, respectively;
(l) SEQ ID NOs: 12, 30, 48, 66, 84, and 102, respectively;
(m) SEQ ID NOs: 13, 31, 49, 67, 85, and 103, respectively;
(n) SEQ ID NOs: 14, 32, 50, 68, 86, and 104, respectively;
(o) SEQ ID NOs: 15, 33, 51, 69, 87, and 105, respectively;
(p) SEQ ID NOs: 16, 34, 52, 70, 88, and 106, respectively;
(q) SEQ ID NOs: 17, 35, 53, 71, 89, and 107, respectively; or
(r) SEQ ID NOs: 18, 36, 54, 72, 90, and 108, respectively.
6 . The method of claim 2 , wherein the VH comprises one or more of
(a) the amino acid sequences of SEQ ID NOs: 109-126 or 310-315 at Kabat positions H31-H37;
(b) the amino acid sequences of SEQ ID NOs: 127-144 or 316-318 at Kabat positions H52-H56; and
(c) the amino acid sequences of SEQ ID NOs: 145-162 at Kabat positions H61-H62; and
wherein the VL comprises one or more of
(d) the amino acid sequences of SEQ ID NOs: 163-180 or 319-324 at Kabat positions L26-L34;
(e) the amino acid sequences of SEQ ID NOs: 181-198 or 325-334 at Kabat positions L49-L56;
(f) the amino acid sequences of SEQ ID NOs: 199-216 or 335-339 at Kabat positions L67-L70; and
(g) the amino acid sequences of SEQ ID NOs: 217-234 at Kabat positions L89-L97.
7 . The method of claim 2 , wherein
(a) the VH comprises an amino acid sequence that is at least 95% 90% identical to any one of SEQ ID NOs: 235-252; and
b) the VL comprises an amino acid sequence that is at least 95% 90% identical to any one of SEQ ID NOs: 253-270.
8 . The method of claim 2 , wherein the VH and VL comprise the amino acid sequences of
(a) SEQ ID NOs: 235 and 253, respectively;
(b) SEQ ID NOs: 236 and 254, respectively;
(c) SEQ ID NOs: 237 and 255, respectively;
(d) SEQ ID NOs: 238 and 256, respectively;
(e) SEQ ID NOs: 239 and 257, respectively;
(f) SEQ ID NOs: 240 and 258, respectively;
(g) SEQ ID NOs: 241 and 259, respectively;
(h) SEQ ID NOs: 242 and 260, respectively;
(i) SEQ ID NOs: 243 and 261, respectively;
(j) SEQ ID NOs: 244 and 262, respectively;
(k) SEQ ID NOs: 245 and 263, respectively;
(l) SEQ ID NOs: 246 and 264, respectively;
(m) SEQ ID NOs: 247 and 265, respectively;
(n) SEQ ID NOs: 248 and 266, respectively;
(o) SEQ ID NOs: 249 and 267, respectively;
(p) SEQ ID NOs: 250 and 268, respectively;
(q) SEQ ID NOs: 251 and 269, respectively; or
(r) SEQ ID NOs: 252 and 270, respectively.
9 . The method of claim 2 , wherein the antibody further comprises a heavy and/or light chain constant region.
10 . The method of claim 2 , wherein the antibody is a chimeric antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody.
11 . The method of claim 3 , wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 comprise the amino acid sequences of
(a) SEQ ID NOs: 1, 19, 37, 55, 73, and 91, respectively;
(b) SEQ ID NOs: 2, 20, 38, 56, 74, and 92, respectively;
(c) SEQ ID NOs: 3, 21, 39, 57, 75, and 93, respectively;
(d) SEQ ID NOs: 4, 22, 40, 58, 76, and 94, respectively;
(e) SEQ ID NOs: 5, 23, 41, 59, 77, and 95, respectively;
(f) SEQ ID NOs: 6, 24, 42, 60, 78, and 96, respectively;
(g) SEQ ID NOs: 7, 25, 43, 61, 79, and 97, respectively;
(h) SEQ ID NOs: 8, 26, 44, 62, 80, and 98, respectively;
(i) SEQ ID NOs: 9, 27, 45, 63, 81, and 99, respectively;
(j) SEQ ID NOs: 10, 28, 46, 64, 82, and 100, respectively;
(k) SEQ ID NOs: 11, 29, 47, 65, 83, and 101, respectively;
(l) SEQ ID NOs: 12, 30, 48, 66, 84, and 102, respectively;
(m) SEQ ID NOs: 13, 31, 49, 67, 85, and 103, respectively;
(n) SEQ ID NOs: 14, 32, 50, 68, 86, and 104, respectively;
(o) SEQ ID NOs: 15, 33, 51, 69, 87, and 105, respectively;
(p) SEQ ID NOs: 16, 34, 52, 70, 88, and 106, respectively;
(q) SEQ ID NOs: 17, 35, 53, 71, 89, and 107, respectively; or
(r) SEQ ID NOs: 18, 36, 54, 72, 90, and 108, respectively.
12 . The method of claim 3 , wherein the VH comprises one or more of
(a) the amino acid sequences of SEQ ID NOs: 109-126 or 310-315 at Kabat positions H31-H37;
(b) the amino acid sequences of SEQ ID NOs: 127-144 or 316-318 at Kabat positions H52-H56; and
(c) the amino acid sequences of SEQ ID NOs: 145-162 at Kabat positions H61-H62; and
wherein the VL comprises one or more of
(d) the amino acid sequences of SEQ ID NOs: 163-180 or 319-324 at Kabat positions L26-L34;
(e) the amino acid sequences of SEQ ID NOs: 181-198 or 325-334 at Kabat positions L49-L56;
(f) the amino acid sequences of SEQ ID NOs: 199-216 or 335-339 at Kabat positions L67-L70; and
(g) the amino acid sequences of SEQ ID NOs: 217-234 at Kabat positions L89-L97.
13 . The method of claim 3 , wherein
(a) the VH comprises an amino acid sequence that is at least 95% 90% identical to any one of SEQ ID NOs: 235-252; and
b) the VL comprises an amino acid sequence that is at least 95% 90% identical to any one of SEQ ID NOs: 253-270.
14 . The method of claim 3 , wherein the VH and VL comprise the amino acid sequences of
(a) SEQ ID NOs: 235 and 253, respectively;
(b) SEQ ID NOs: 236 and 254, respectively;
(c) SEQ ID NOs: 237 and 255, respectively;
(d) SEQ ID NOs: 238 and 256, respectively;
(e) SEQ ID NOs: 239 and 257, respectively;
(f) SEQ ID NOs: 240 and 258, respectively;
(g) SEQ ID NOs: 241 and 259, respectively;
(h) SEQ ID NOs: 242 and 260, respectively;
(i) SEQ ID NOs: 243 and 261, respectively;
(j) SEQ ID NOs: 244 and 262, respectively;
(k) SEQ ID NOs: 245 and 263, respectively;
(l) SEQ ID NOs: 246 and 264, respectively;
(m) SEQ ID NOs: 247 and 265, respectively;
(n) SEQ ID NOs: 248 and 266, respectively;
(o) SEQ ID NOs: 249 and 267, respectively;
(p) SEQ ID NOs: 250 and 268, respectively;
(q) SEQ ID NOs: 251 and 269, respectively; or
(r) SEQ ID NOs: 252 and 270, respectively.
15 . The method of claim 3 , wherein the antibody further comprises a heavy and/or light chain constant region.
16 . The method of claim 3 , wherein the antibody is a chimeric antibody, an antibody fragment, a bispecific antibody, or a trispecific antibody.