Anti-Hemagglutinin Antibody Compositions and Methods of Use Thereof

Abstract

The present invention provides novel human anti-Influenza antibodies and related compositions and methods. These antibodies are used in the prevention, inhibition, neutralization, diagnosis, and treatment of influenza infection.

What is claimed is: 
     
         1 . An isolated fully human monoclonal antibody, wherein said monoclonal antibody has the following characteristics:
 a) binds to an influenza A virus;   b) binds to a cell contacted with influenza A;   c) binds to an epitope of an influenza A viral protein; and   d) neutralizes influenza A virus infection.   
     
     
         2 . The antibody of  claim 1 , wherein said influenza A viral protein is hemagglutinin (HA). 
     
     
         3 . The antibody of  claim 2 , wherein said hemagglutinin (HA) comprises a hemagglutinin precursor peptide (HA0), a HA1 subunit, a HA2 subunit, a mature protein containing HA1 and HA2, or a recombinant HA polypeptide. 
     
     
         4 . The antibody of  claim 3 , wherein recombinant HA polypeptide is encoded by the sequence of SEQ ID NO: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19. 
     
     
         5 . The antibody of  claim 1 , wherein said antibody is isolated from a B-cell that is isolated from a human donor. 
     
     
         6 . The antibody of  claim 1 , wherein said epitope is linear or non-linear. 
     
     
         7 . The antibody of  claim 6 , wherein said non-linear epitope is a discontinuous epitope. 
     
     
         8 . The antibody of  claim 1 , wherein said antibody is (a) TCN-522 (3212_I12), TCN-521 (3280_D18), TCN-523 (5248_A17), TCN-563 (5237_B21), TCN-526 (5084_C17), TCN-527 (5086_C06), TCN-528 (5087_P17), TCN-529 (5297_H01), TCN-530 (5248_H10), TCN-531 (5091_H13), TCN-532 (5262_H18), TCN-533 (5256_A17a), TCN-534 (5249_B02), TCN-535 (5246_P19), TCN-536 (5095_N01), TCN-537 (3194_D21), TCN-538 (3206_O17), TCN-539 (5056_A08), TCN-540 (5060_F05), TCN-541 (5062_M11), TCN-542 (5079_A16), TCN-543 (5081_G23), TCN-544 (5082_A19), TCN-545 (5082_I15), TCN-546 (5089_L08), TCN-547 (5092_F11), TCN-548 (5092_P01), TCN-549 (5092_P04), TCN-550 (5096_F06), TCN-551 (5243_D01), TCN-552 (5249_I23), TCN-553 (5261_C18), TCN-554 (5277_M05), TCN-555 (5246_L16), TCN-556 (5089_K12), TCN-557 (5081_A04), TCN-558 (5248_H10b), TCN-559 (5097_G08), TCN-560 (5084_P10), TCN-564 (5256_A17b), or TCN-504 (3251_K17), or (b) an antibody that binds the same epitope as TCN-522 (3212_I12), TCN-521 (3280_D18), TCN-523 (5248_A17), TCN-563 (5237_B21), TCN-526 (5084_C17), TCN-527 (5086_C06), TCN-528 (5087_P17), TCN-529 (5297_H01), TCN-530 (5248_H10), TCN-531 (5091_H13), TCN-532 (5262_H18), TCN-533 (5256_A17a), TCN-534 (5249_B02), TCN-535 (5246_P19), TCN-536 (5095_N01), TCN-537 (3194_D21), TCN-538 (3206_O17), TCN-539 (5056_A08), TCN-540 (5060_F05), TCN-541 (5062_M11), TCN-542 (5079_A16), TCN-543 (5081_G23), TCN-544 (5082_A19), TCN-545 (5082_I15), TCN-546 (5089_L08), TCN-547 (5092_F11), TCN-548 (5092_P01), TCN-549 (5092_P04), TCN-550 (5096_F06), TCN-551 (5243 D01), TCN-552 (5249_I23), TCN-553 (5261_C18), TCN-554 (5277_M05), TCN-555 (5246_L16), TCN-556 (5089_K12), TCN-557 (5081_A04), (5248_H10b), TCN-559 (5097_G08), TCN-560 (5084_P10), TCN-564 (5256_A17b), or TCN-504 (3251_K17). 
     
     
         9 . An isolated anti-hemagglutinin (HA) antibody, wherein said antibody comprises a combination of variable heavy chain complementarity determining region 1 (VH CDR1), variable heavy chain complementarity determining region 2 (VH CDR2), variable heavy chain complementarity determining region 3 (VH CDR3), variable light chain complementarity determining region 1 (VL CDR1), variable light chain complementarity determining region 2 (VL CDR2), and variable light chain complementarity determining region 3 (VL CDR3), selected from the group consisting of:
 (a) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 511;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 512, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 513, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 517; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 181, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 518; 
   (b) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 22;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 23, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 24, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 29; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 30, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 31; 
   (c) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 34;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 35, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 36, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 41; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 42, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 43; 
   (d) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 46;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 47, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 48, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 53; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 54, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 55; 
   (e) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 62;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 58, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 59, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 65; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 66, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 67; 
   (f) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 70;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 71, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 72, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 77; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 78, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 79; 
   (g) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 82;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 83, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 84, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 89; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 90, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 91; 
   (h) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 94;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 95, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 96, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 101; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 102, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 103; 
   (i) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 106;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 107, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 108, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 113; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 114, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 115; 
   (j) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 118;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 119, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 120, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 125; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 126, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 127; 
   (k) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 130;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 131, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 132, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 137; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 138, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 139; 
   (l) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 142;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 143, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 144, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 149; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 150, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 151; 
   (m) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 154;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 155, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 156, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 53; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 54, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 55; 
   (n) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 162;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 163, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 164, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 169; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 170, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 171; 
   (o) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 174;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 175, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 176, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 157; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 181, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 182; 
   (p) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 185;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 186, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 187, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 192; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 30, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 193; 
   (q) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 196;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 197, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 198, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 203; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 204, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 205; 
   (r) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 208;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 209, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 210, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 215; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 216, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 217; 
   (s) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 220;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 221, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 222, 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 227; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 228, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 229; 
   (t) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 232;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 233, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 234; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 239; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 240, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 241; 
   (u) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 244;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 245, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 246; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 251; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 252, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 253; 
   (v) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 256;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 257, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 258; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 263; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 264, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 265; 
   (w) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 268;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 269, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 270; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 275; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 276, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 277; 
   (x) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 280;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 281, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 282; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 287; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 288, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 289; 
   (y) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 292;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 293, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 294; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 299; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 181, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 300; 
   (z) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 303;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 304, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 305; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 310; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 30, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 311; 
   (aa) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 314;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 315, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 316; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 321; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 322, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 323; 
   (bb) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 303;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 326, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 327; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 332; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 216, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 333; 
   (cc) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 336;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 337, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 338; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 343; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 216, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 344; 
   (dd) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 347;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 348, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 349; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 354; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 355, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 356; 
   (ee) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 359;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 360, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 361; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 366; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 367, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 368; 
   (ff) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 371;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 372, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 373; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 378; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 379, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 380; 
   (gg) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 383;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 384, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 385; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 203; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 181, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 390; 
   (hh) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 393;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 394, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 395; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 400; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 216, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 401; 
   (ii) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 62;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 58, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 59; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 406; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 66, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 67; 
   (jj) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 409;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 410, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 411; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 416; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 417, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 418; 
   (kk) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 421;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 422, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 423; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 428; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 429, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 430; 
   (ll) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 174;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 175, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 176; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 125; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 126, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 127; 
   (mm) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 435;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 436, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 437; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 442; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 443, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 444; 
   (nn) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 447;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 448, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 449; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 454; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 455, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 456; and 
   (oo) a VH CDR1 region comprising the amino acid sequence of SEQ ID NO: 154;
 a VH CDR2 region comprising the amino acid sequence of SEQ ID NO: 155, 
 a VH CDR3 region comprising the amino acid sequence of SEQ ID NO: 156; 
 a VL CDR1 region comprising the amino acid sequence of SEQ ID NO: 520; 
 a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 521, and 
 a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 522. 
   
     
     
         10 . An isolated fully human monoclonal anti-hemagglutinin (HA) antibody comprising:
 a) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 510 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 524 or   b) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 21 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 28 or   c) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 33 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 40 or   d) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 45 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 52 or   e) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 57 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 64 or   f) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 69 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 76 or   g) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 81 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 88 or   h) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 93 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 100 or   i) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 105 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 112 or   j) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 117 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 124 or   k) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 129 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 136 or   l) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 141 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 148 or   m) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 52 or   n) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 161 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 168 or   o) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 173 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 180 or   p) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 184 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 191 or   q) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 195 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 202 or   r) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 207 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 214 or   s) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 219 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 226 or   t) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 231 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 238 or   u) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 243 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 250 or   v) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 255 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 262 or   w) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 267 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 274 or   x) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 279 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 286 or   y) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 291 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 298 or   z) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 302 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 309 or   aa) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 313 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 320 or   bb) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 325 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 331 or   cc) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 335 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 342 or   dd) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 346 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 353 or   ee) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 358 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 365 or   ff) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 370 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 377 or   gg) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 382 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 389 or   hh) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 392 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 399 or   ii) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 403 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 405 or   jj) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 420 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 427 or   kk) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 173 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 124 or   ll) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 434 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 441 or   mm) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 446 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 453 or   nn) a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable sequence comprising amino acid sequence SEQ ID NO: 519.   
     
     
         11 . The antibody of  claim 1 , wherein said cell is a eukaryotic cell. 
     
     
         12 . The antibody of  claim 1 , wherein said cell is a human cell. 
     
     
         13 . The antibody of  claim 1 , wherein said antibody is operably-linked to a therapeutic agent or a detectable label. 
     
     
         14 . A pharmaceutical composition comprising the antibody of  claim 1  and a pharmaceutical carrier. 
     
     
         15 . The composition of  claim 14 , further comprising an anti-viral drug, a viral entry inhibitor or a viral attachment inhibitor. 
     
     
         16 . The composition of  claim 15 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel inhibitor. 
     
     
         17 . The composition of  claim 16 , wherein said M2 ion channel inhibitor is amantadine or rimantadine. 
     
     
         18 . The composition of  claim 16 , wherein said neuraminidase inhibitor zanamivir or oseltamivir phosphate. 
     
     
         19 . The composition of  claim 14 , further comprising a second anti-Influenza A antibody. 
     
     
         20 . A method for stimulating an immune response in a subject, comprising administering to the subject the pharmaceutical composition of  claim 14 . 
     
     
         21 . A method for the treatment of an Influenza virus infection in a subject, comprising administering to the subject the pharmaceutical composition of  claim 14 . 
     
     
         22 . A method for the prevention of an Influenza virus infection in a subject, comprising administering to the subject the composition of  claim 14  prior to exposure of the subject to Influenza virus or infection. 
     
     
         23 . The method of  claim 21 , wherein the method further comprises administering an anti-viral drug, a viral entry inhibitor, a viral attachment inhibitor, or a second anti-Influenza A antibody. 
     
     
         24 . The method of  claim 23 , wherein said anti-viral drug is a neuraminidase inhibitor, a HA inhibitor, a sialic acid inhibitor or an M2 ion channel. 
     
     
         25 . The method of  claim 24 , wherein said M2 ion channel inhibitor is amantadine or rimantadine. 
     
     
         26 . The method of  claim 24 , wherein said neuraminidase inhibitor zanamivir or oseltamivir phosphate. 
     
     
         27 . The method of  claim 21 , wherein said antibody is administered prior to or after exposure to Influenza virus. 
     
     
         28 . The method of  claim 21 , wherein said antibody is administered at a dose sufficient to promote viral clearance or eliminate Influenza A infected cells. 
     
     
         29 . A method for determining the presence of an Influenza virus infection in a subject, comprising the steps of:
 (a) contacting a biological sample obtained from the subject with the antibody of  claim 1 ;   (b) detecting an amount of the antibody that binds to the biological sample; and   (c) comparing the amount of antibody that binds to the biological sample to a control value, and therefrom determining the presence of the Influenza virus in the subject.   
     
     
         30 . A vaccine composition comprising the antibody of  claim 1  or an epitope bound by the antibody of  claim 1 . 
     
     
         31 . A diagnostic kit comprising the antibody of  claim 1 . 
     
     
         32 . A prophylactic kit comprising the antibody of  claim 1  or an epitope bound by the antibody of  claim 1 .