Neoantigen expression in ovarian cancer and uses thereof

Abstract

The present disclosure relates to ovarian cancer neoantigens, polynucleotides encoding same, vectors, host cells, recombinant viral particles, vaccines comprising said neoantigens, proteinaceous molecules that bind to said ovarian cancer neoantigens, and methods of making and using same.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 62 / 976,384, filed February 14, 2020, entitled "NEOANTIGENS EXPRESSED IN OVARIAN CANCER AND THEIR USES," which is incorporated by reference in its entirety.

[0002] (Sequence Listing) This application contains a Sequence Listing that has been submitted electronically in ASCII format, which is incorporated herein by reference in its entirety. The ASCII copy was created on January 22, 2021, is named JBI6238WOPCT1_SL.txt, and is 165,739 bytes in size.

[0003] FIELD OF THE INVENTION The present disclosure relates to ovarian cancer neoantigens, polynucleotides encoding same, vectors, host cells, vaccines comprising said neoantigens, proteinaceous molecules that bind to said ovarian cancer neoantigens, and methods of making and using same. [Background technology]

[0004] Ovarian cancer is the fifth leading cause of cancer-related death in women. A woman's lifetime risk of developing ovarian cancer is approximately 1 in 78. The American Cancer Society predicts that in 2020, there will be approximately 21,750 new cases of ovarian cancer and 13,940 deaths from the disease in the United States.

[0005] Ovarian cancer develops due to the uncontrolled growth of abnormal cells in the inner, proximal, or outer layers of the ovaries. Surgery to remove the cancerous growth is the most common treatment for ovarian cancer. Surgical procedures may include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, visualization of the entire peritoneal surface, and random peritoneal biopsies and peritoneal washings. After surgery, adjuvant chemotherapy is mandatory for suboptimal debulking (residual disease ≥1 cm), advanced stage, or early stage disease with a high risk of recurrence. Since the early 2000s, platinum-paclitaxel chemotherapy combinations have been the standard of care in the adjuvant and first-line settings.

[0006] First-line treatment with platinum-paclitaxel chemotherapy combinations has been shown to have a response rate of over 80% in patients with advanced ovarian cancer, but most patients ultimately relapse, with a median progression-free survival of 18 months. Resistance to platinum-based chemotherapy is the primary cause of the reduced overall survival associated with ovarian cancer. Response rates to second-line agents, such as liposomal doxorubicin, gemcitabine, or topotecan, decrease with each subsequent relapse due to chemoresistance, resulting in a 5-year overall survival rate of 30–40%. Summary of the Invention [Problem to be solved by the invention]

[0007] Thus, there remains a need for treatments for ovarian cancer, including relapsed, refractory, and / or platinum-resistant ovarian cancer. [Means for solving the problem]

[0008] The present disclosure provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 3, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223 , 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, or a fragment thereof.

[0009] The present disclosure also provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 25, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227 , 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, and fragments thereof.

[0010] The present disclosure also relates to SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122 , 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 3 24, 326, 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, or 406, or a fragment thereof.

[0011] The present disclosure also provides vectors comprising a polynucleotide encoding a polypeptide disclosed herein.

[0012] The present disclosure also provides a virus or recombinant virus comprising a vector of the present disclosure.

[0013] The present disclosure also provides a self-replicating RNA molecule comprising a vector of the present disclosure.

[0014] The present disclosure also provides cells comprising or transduced with a vector of the present disclosure or a recombinant virus of the present disclosure.

[0015] The present disclosure also provides a vaccine comprising a polynucleotide of the present disclosure.

[0016] The present disclosure also provides vaccines comprising the polypeptides of the present disclosure.

[0017] The present disclosure also provides a vaccine comprising the vector of the present disclosure.

[0018] The present disclosure also provides a vaccine comprising the recombinant virus of the present disclosure.

[0019] The present disclosure also provides a vaccine comprising the self-replicating RNA molecule of the present disclosure.

[0020] The present disclosure also provides methods for treating or preventing ovarian cancer in a subject, comprising administering to the subject a therapeutically effective amount of one or more vaccines of the present disclosure, one or more viruses or recombinant viruses of the present disclosure, or one or more pharmaceutical compositions of the present disclosure.

[0021] The present disclosure also provides a method for detecting and / or treating a subject with SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175 5, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 25 1, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 366 7, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, comprising administering to the subject one or more recombinant viruses of the present disclosure comprising a polynucleotide of the present disclosure, and / or administering a self-replicating RNA molecule encoding a polypeptide of the present disclosure, wherein the recombinant virus is Ad26, GAd20, MVA.

[0022] The present disclosure also provides a method of treating or preventing ovarian cancer in a subject, comprising:a therapeutically effective amount of a composition comprising a recombinant virus and / or a sequence encoding SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 2 01, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 26 3, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325 , 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 17 12, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148 , 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 1 Methods are provided, comprising administering to a subject a therapeutically effective amount of a composition comprising a self-replicating RNA molecule encoding a heterologous polypeptide, the heterologous polypeptide comprising 85, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, or 203 polypeptides. In some embodiments, the recombinant virus is Ad26, GAd20, or MVA virus. In some embodiments, the administration comprises one or more administrations.

[0023] The present disclosure also provides a method of treating or preventing ovarian cancer in a subject, comprising: A first composition comprising a first heterologous polynucleotide encoding a first heterologous polypeptide, wherein the first heterologous polypeptide is selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 1 05, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 2 13, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 3 a first composition comprising two or more polypeptides selected from the group consisting of 21, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, and 405, and fragments thereof; A second composition comprising a second heterologous polynucleotide encoding a second heterologous polypeptide, wherein the second heterologous polypeptide is selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 1 05, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 2 13, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 3 a second composition comprising two or more polypeptides selected from the group consisting of 21, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, and 405, and fragments thereof; to a subject, wherein the first heterologous polypeptide and the second heterologous polypeptide have different amino acid sequences.

[0024] The present disclosure also provides a method of treating or preventing ovarian cancer in a subject, comprising administering to a subject a therapeutically effective amount of a composition comprising a recombinant virus and / or a recombinant human ovarian cancer vaccine comprising SEQ ID NOs: 1, 3, 5, 11, 15, 17, 19, 21, 25, 29, 31, 33, 39, 43, 45, 49, 53, 59, 63, 65, 67, 81, 85, 87, 89, 91, 95, 97, 111, 113, 115, 119, 123, 127, 129, 145, 177, 179, 181, 183, 185, 187, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 212, 214, 216, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 2 15, 219, 221, 223, 229, 233, 235, 237, 239, 241, 243, 245, 247, 251, 255, 257, 259, 261, 263, 267, 271, 279, 281, 285, 293, 295, 297, 301, 303, 305, 307, 309, 319, 323, 325, 337, 339, 343, 345, 349, 371, and 375, and fragments thereof, are provided.

[0025] The present disclosure also provides for administering an anti-CTLA-4 antibody, anti-PD-1, or anti-PD-L1 antibody in combination with any of the compositions comprising the polynucleotides, polypeptides, vectors, or viruses disclosed herein.

[0026] It should be understood that the above-described embodiments of the invention encompass polypeptides that include, in addition to the specifically recited polypeptides and fragments thereof, additional polypeptide sequences that include one or more polypeptides different from those specifically recited. Similarly, the above-described embodiments of the invention encompass polynucleotides that include, in addition to the specifically recited polynucleotides and fragments thereof, additional polynucleotide sequences that include one or more polynucleotides different from those specifically recited. [Brief explanation of the drawings]

[0027] [Figure 1]A schematic diagram of the gene fusion resulting from the chimeric read-through fusion is shown, with the neo-antigenic peptide sequence occurring at the breakpoint junction. [Figure 2] A schematic diagram of gene fusions resulting from chromosomal alterations such as DNA translocations is shown. [Figure 3] Schematic representations of splice variants with alternative 5' or 3' splice sites, retained introns, omitted exons, or alternative stops or insertions are shown. [Figure 4] A schematic diagram of the approach to identifying splice variants is shown. [Figure 5A] A heatmap showing tumor-restricted expression of candidate ovarian cancer neoantigens is shown. These antigens have no detectable expression in either healthy tissue or immune cells derived from healthy donors. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 5B] A heatmap showing tumor-restricted expression of candidate ovarian cancer neoantigens is shown. These antigens have no detectable expression in either healthy tissue or immune cells derived from healthy donors. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 5C]A heatmap showing tumor-restricted expression of candidate ovarian cancer neoantigens is shown. These antigens have no detectable expression in either healthy tissue or immune cells derived from healthy donors. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 5D] A heatmap showing tumor-restricted expression of candidate ovarian cancer neoantigens is shown. These antigens have no detectable expression in either healthy tissue or immune cells derived from healthy donors. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 6A] A heatmap representing candidate ovarian cancer neoantigens expressed in both control (tissues and immune cells from healthy donors) and tumor samples is shown. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 6B]A heatmap representing candidate ovarian cancer neoantigens expressed in both control (tissues and immune cells from healthy donors) and tumor samples is shown. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 6C] A heatmap representing candidate ovarian cancer neoantigens expressed in both control (tissues and immune cells from healthy donors) and tumor samples is shown. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 6D] A heatmap representing candidate ovarian cancer neoantigens expressed in both control (tissues and immune cells from healthy donors) and tumor samples is shown. Immune cell types (first 15 rows) were derived from three healthy donors (donor IDs: D001003103, D001000682, and D001004622). Ovarian cancer samples are prefixed with "OV_CA." Raw Ct values ​​were normalized to the expression of the endogenous control gene, RPL19. Black cells represent high expression (ΔCt < 15) in each sample. [Figure 7A] Representative dot plots illustrating positive immunogenic responses to neoantigens using an exogenous autologous healthy donor restimulation assay are shown. Immunogenic responses were measured by estimating IFNγ TNFα double-positive cells in the CD4+ and / or CD8+ cell populations. Responses were considered positive if the IFNγ TNFα double-positive fraction was 3-fold or greater over unstimulated cells (DMSO negative control) and had a minimum frequency of 0.01% or greater. [Figure 7B]Representative dot plots illustrating positive immunogenic responses to neoantigens using an exogenous autologous healthy donor restimulation assay are shown. Immunogenic responses were measured by estimating IFNγ TNFα double-positive cells in the CD4+ and / or CD8+ cell populations. Responses were considered positive if the IFNγ TNFα double-positive fraction was 3-fold or greater over unstimulated cells (DMSO negative control) and had a minimum frequency of 0.01% or greater. [Figure 8] The number of donors with a positive immunogenic response (CD8+ and / or CD4+ T cells) to the gene fusion-associated neoantigens is shown. [Figure 9A] Figures 9A and 9B show the number of donors with a positive immunogenic response (CD8+ and / or CD4+ T cells) against alternative splicing-associated neoantigens. [Figure 9B] Figures 9A and 9B show the number of donors with a positive immunogenic response (CD8+ and / or CD4+ T cells) against alternative splicing-associated neoantigens. DETAILED DESCRIPTION OF THE INVENTION

[0028] definition All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as if fully set forth.

[0029] It should be understood that the terms used herein are used for the purpose of describing particular embodiments only and are not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0030] Although any methods and materials similar or equivalent to those described herein can be used in the practice for testing of the present disclosure, exemplary materials and methods are described herein. In describing and claiming the present disclosure, the following terminology will be used.

[0031] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a cell" includes a combination of two or more cells, and the like.

[0032] The transitional phrases "comprising," "consisting essentially of," and "consisting" are intended to connote their generally accepted meanings in patent language, i.e., (i) "comprising" is synonymous with "comprising," "containing," or "characterized by" and is inclusive or open-ended and does not exclude other unrecited elements or method steps; (ii) "consisting of" excludes any element, step, or ingredient not specified in the claim; and (iii) "consisting essentially of" limits the scope of the claim to the specified materials or steps and those that "do not materially affect the basic and novel characteristics" of the claimed disclosure. Embodiments described with the phrase "comprising" (or its equivalents) also provide those described independently with the phrases "consisting of" and "consisting essentially of," as embodiments.

[0033] As used herein and in the appended claims, the phrase "and fragments thereof," when attached to a list, includes all members of the associated list. A list may include Markush groups, such as, for example, the phrase "the group consisting of peptides A, B, and C and fragments thereof" specifies or recites a Markush group that includes A, B, C, fragments of A, fragments of B, and fragments of C.

[0034] "Isolated" refers to a homogenous population of molecules that have been substantially separated and / or purified away from other components of the system in which they are produced, such as in a recombinant cell (e.g., a synthetic polynucleotide or polypeptide), as well as to proteins that have been subjected to at least one purification or isolation step. "Isolated" refers to molecules that are substantially free of other cellular material and / or chemicals and includes molecules isolated to greater degrees of purity, for example, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% purity.

[0035] "Polynucleotide" refers to a synthetic molecule comprising a chain of nucleotides covalently linked by a sugar-phosphate backbone or other equivalent covalent chemistry.

[0036] A "polypeptide" or "protein" refers to a molecule comprising at least two amino acid residues linked by a peptide bond to form the polypeptide.

[0037] An "immunogenic fragment" refers to a polypeptide that is recognized by cytotoxic T lymphocytes, helper T lymphocytes, or B cells when the fragment is in a complex with an MHC class I or MHC class II molecule.

[0038] "In-frame" refers to the codon reading frame in a first polynucleotide being the same as the codon reading frame in a second polynucleotide that are joined together to form a heterologous polynucleotide. An in-frame heterologous polynucleotide encodes a heterologous polypeptide that is encoded by both the first and second polynucleotides.

[0039] "Immunogenic" refers to a polypeptide that comprises one or more immunogenic fragments.

[0040] "Heterologous" refers to two or more polynucleotides or two or more polypeptides that are not found in the same relationship to each other in nature.

[0041] A "heterologous polynucleotide" refers to a non-naturally occurring polynucleotide that encodes two or more neo-antigens described herein.

[0042] A "heterologous polypeptide" refers to a non-naturally occurring polypeptide that comprises two or more neoantigen polypeptides described herein.

[0043] "Non-naturally occurring" refers to a molecule that does not exist in nature.

[0044] A "vector" refers to a polynucleotide that can be replicated within a biological system or transferred between such systems. Vector polynucleotides typically contain elements such as an origin of replication, a polyadenylation signal, or a selectable marker that function to facilitate the replication or maintenance of these polynucleotides within a biological system. Examples of such biological systems include cells, viruses, animals, plants, and reconstituted biological systems that utilize biological components capable of replicating the vector. The polynucleotides that make up a vector can be DNA or RNA molecules, or hybrid molecules thereof.

[0045] An "expression vector" refers to a vector that can be utilized in a biological system or reconstituted biological system to direct the translation of a polypeptide encoded by a polynucleotide sequence present in the expression vector.

[0046] A "viral vector" refers to a vector construct that contains at least one polynucleotide element of viral origin and is capable of being packaged into a viral vector particle.

[0047] "Neoantigen" refers to a polypeptide present in ovarian tumor tissue that has at least one alteration that makes it different from the corresponding wild-type polypeptide present in non-malignant tissue, e.g., through a mutation in the tumor cell or a tumor cell-specific post-translational modification. Mutations can include frameshift or non-frameshift insertions or deletions, missense or nonsense substitutions, splice site alterations, aberrant splice variants, genomic rearrangements or gene fusions, or any genomic or expression alteration that gives rise to a neoantigen.

[0048] "Prevalence" refers to the proportion of the population studied that carries the ovarian neoantigen.

[0049] "Recombinant" refers to polynucleotides, polypeptides, vectors, viruses, and other macromolecules that are prepared, expressed, produced, or isolated by recombinant means.

[0050] "Vaccine" refers to a composition comprising one or more immunogenic polypeptides, immunogenic polynucleotides or fragments, or any combination thereof, intentionally administered to a recipient (e.g., a subject) to induce adaptive immunity.

[0051] "Treating," "treating," or "treatment" of a disease or disorder, such as cancer, hereinafter refers to achieving one or more of: reducing the severity and / or duration of the disorder; inhibiting the worsening of symptoms characteristic of the disorder being treated; limiting or preventing the recurrence of the disorder in a subject who previously had the disorder; or limiting or preventing the recurrence of symptoms in a subject who was previously symptomatic for the disorder.

[0052] "Preventing," "preventing," "prevention," or "prophylaxis" of a disease or disorder means preventing the disorder from occurring in a subject.

[0053] A "therapeutically effective amount" refers to an amount effective to obtain a desired therapeutic result at the dosage and for the period required. A therapeutically effective amount may vary depending on factors such as the individual's condition, age, sex, and weight, as well as the ability of a single therapeutic agent or combination of therapeutic agents to elicit a desired response in an individual. Exemplary indicators of an effective single therapeutic agent or combination of therapeutic agents include, for example, improved health of the patient.

[0054] "Relapse" refers to the return of a disease or signs and symptoms of a disease after a period of improvement following prior treatment with a therapeutic agent.

[0055] "Refractory" refers to a disease that does not respond to treatment. A refractory disease can be resistant to treatment before or at the start of treatment, or a refractory disease can become resistant during treatment.

[0056] A "replicon" refers to viral nucleic acid, including RNA and DNA, that can direct the production of copies of itself. For example, a double-stranded DNA version of an arterivirus genome can be used to generate the single-stranded RNA transcripts that constitute the arterivirus replicon. Generally, a viral replicon contains the complete genome of the virus. A "subgenomic replicon" refers to viral nucleic acid that contains less than the full complement of genes and other machinery of the viral genome but is still capable of directing the production of copies of itself. For example, an arterivirus subgenomic replicon may contain most of the genes for the virus's nonstructural proteins but lack most of the genes encoding the structural proteins. A subgenomic replicon can direct the expression of all of the viral genes necessary for viral subgenome replication (subgenomic replicon replication) without producing viral particles.

[0057] An "RNA replicon" (or "self-replicating RNA molecule") refers to an RNA that contains all of the genetic information required to direct its own amplification or self-replication in a permissive cell. To direct its own replication, the RNA molecule 1) encodes a polymerase, replicase, or other protein that can interact with proteins, nucleic acids, or ribonucleoproteins derived from the virus or host cell to catalyze the RNA amplification process, and 2) contains cis-acting RNA sequences necessary for the replication and transcription of the replicon-encoding RNA. Self-replicating RNAs are typically derived from the genome of positive-strand RNA viruses and can be used as the basis for introducing foreign sequences into host cells by replacing viral sequences encoding structural or nonstructural genes or by inserting foreign sequences 5' or 3' to sequences encoding structural or nonstructural genes. Foreign sequences can also be introduced into the subgenomic region of an alphavirus. Self-replicating RNAs can be packaged into recombinant viral particles, such as recombinant alphavirus particles, or delivered to the host using lipid nanoparticles (LNPs). The self-replicating RNA may be at least 1 kb, or at least 2 kb, or at least 3 kb, or at least 4 kb, or at least 5 kb, or at least 6 kb, or at least 7 kb, or at least 8 kb, or at least 10 kb, or at least 12 kb, or at least 15 kb, or at least 17 kb, or at least 19 kb, or at least 20 kb in size, or may be 100 bp to 8 kb, or 500 bp to 8 kb, or 500 bp to 7 kb, or 1 to 7 kb, or 1 to 8 kb, or 2 to 15 kb, or 2 to 20 kb, or 5 to 15 kb, or 5 to 20 kb, or 7 to 15 kb, or 7 to 18 kb, or 7 to 20 kb in size. Self-replicating RNAs are described, for example, in WO 2017 / 180770, WO 2018 / 075235, and WO 2019143949(A2).

[0058] A "subject" includes any human or non-human animal. A "non-human animal" includes all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cats, horses, cows, chickens, amphibians, reptiles, etc. The terms "subject" and "patient" can be used interchangeably herein.

[0059] "In combination with" means that two or more therapeutic agents are administered to a subject together in an admixture, simultaneously as single agents, or sequentially as single agents in any order.

[0060] "Enhancing" or "inducing," in reference to an immune response, refers to increasing the scale and / or efficiency of an immune response or extending the duration of an immune response. These terms are used interchangeably with "boosting."

[0061] "Immune response" refers to any response by the immune system of a vertebrate subject to an immunogenic polypeptide or polynucleotide or fragment. Exemplary immune responses include local and systemic cellular and humoral immunity, e.g., CD8 + These include CTL responses, which include antigen-specific induction of cytotoxic T lymphocytes (CTLs), helper T cell responses, which include T cell proliferative responses and cytokine release, and B cell responses, which include antibody responses.

[0062] "Specifically binds," "specific binding," "specifically binding," or "binds" refers to a proteinaceous molecule binding to an antigen or an epitope within the antigen (e.g., an ovarian neoantigen) with higher affinity than its affinity for other antigens. Typically, a proteinaceous molecule binds to an antigen with an affinity of about 1 x 10 -7 M or less, e.g., about 5 × 10 -8 M or less, approximately 1×10 -8 M or less, approximately 1×10 -9 M or less, approximately 1×10 -10 M or less, approximately 1×10 -11 M or less, or about 1 x 10 -12 The equilibrium dissociation constant (K D) binds to an antigen or an epitope within the antigen, typically D is the K for binding to nonspecific antigens (e.g., BSA, casein) D In the context of the ovarian neoantigens described herein, "specific binding" refers to the binding of a proteinaceous molecule to an ovarian neoantigen without detectably binding to the wild-type protein of which the ovarian neoantigen is a variant.

[0063] "Variant," "mutant," or "altered" refers to a polypeptide or polynucleotide that differs from a reference polypeptide or polynucleotide by one or more modifications, e.g., one or more substitutions, insertions, or deletions.

[0064] "Antibody" refers to immunoglobulin molecules, including monoclonal antibodies, including murine, human, humanized, and chimeric monoclonal antibodies, antigen-binding fragments, bispecific or multispecific antibodies, dimeric, tetrameric, or multimeric antibodies, single-chain antibodies, domain antibodies, and any other modified configuration of immunoglobulin molecules that contain an antigen-binding site of the required specificity.

[0065] "Alternative scaffold" refers to a single-chain protein framework containing a structured core associated with conformationally tolerant variable domains that can be engineered and selected to bind specific antigens because the variable domains tolerate polymorphism introduced without compromising the integrity of the scaffold.

[0066] "Chimeric antigen receptor" or "CAR" refers to a genetically engineered T cell receptor (e.g., naive T cells, central memory T cells, effector memory T cells, or a combination thereof) that transfers ligand or antigen specificity onto a T cell. CARs are also known as artificial T cell receptors, chimeric T cell receptors, or chimeric immune receptors. CARs comprise an extracellular domain capable of binding to an antigen, a transmembrane domain, and at least one intracellular domain. The CAR intracellular domain comprises a polypeptide known to function as a domain that transmits a signal that causes activation or inhibition of a biological process within the cell. The transmembrane domain comprises any peptide or polypeptide known to span the cell membrane and that can function to connect the extracellular domain and the signaling domain. Chimeric antigen receptors may optionally comprise a hinge domain that functions as a linker between the extracellular domain and the transmembrane domain.

[0067] "T cell receptor" or "TCR" refers to a molecule capable of recognizing peptides when presented by MHC molecules. Naturally occurring TCR heterodimers consist of an alpha (α) chain and a beta (β) chain in approximately 95% of T cells, while approximately 5% of T cells have TCRs consisting of a gamma (γ) chain and a delta (δ) chain. Each chain of a natural TCR is a member of the immunoglobulin superfamily and has one N-terminal immunoglobulin (Ig) variable (V) domain, one Ig constant (C) domain, a transmembrane / transmembrane region, and a short cytoplasmic tail at the C-terminus. The variable domains of both the α and β chains of the TCR contain three hypervariable or complementarity-determining regions (CDRs), CDR1, CDR2, and CDR3, which are responsible for recognizing processed antigens presented on MHC.

[0068] The TCR may be a full-length α / β or γ / δ heterodimer, or may be a soluble molecule comprising a portion of the extracellular domain of the TCR that retains binding of the peptide / MHC complex. The TCR may also be genetically engineered into a single-chain TCR.

[0069] "T cell receptor complex" or "TCR complex" refers to the known TCR complex, which is composed of TCRα and TCRβ chains, CD3ε, CD3γ, CD3δ, and CD3ζ molecules. In some instances, the TCRα and TCRβ chains are replaced by TCRγ and TCRδ chains. The amino acid sequences of the various proteins that form the TCR complex are well known.

[0070] "T cells" and "T lymphocytes" are interchangeable and are used synonymously herein. T cells include thymocytes, naive T lymphocytes, memory T cells, immature T lymphocytes, mature T lymphocytes, resting T lymphocytes, or activated T lymphocytes. T cells can be T helper (Th) cells, e.g., T helper 1 (Th1) or T helper 2 (Th2) cells. T cells can be T helper cells (HT1, CD4 + T cells), CD4 + T cells, cytotoxic T cells (CTL, CD8 + T cells), tumor-infiltrating cytotoxic T cells (TIL, CD8 + T cells), CD4 + CD8 + They may be T cells or any other subset of T cells. Also included are "NKT cells," which refers to a specialized population of T cells that not only express the semi-invariant αβ T cell receptor, but also express various molecular markers typically associated with NK cells, such as NK1.1. NKT cells include: + and NK1.1 - , and CD4 + , CD4 - , CD8 + and CD8 -These include NKT cells. The TCR of NKT cells is unique in that it recognizes glycolipid antigens presented by the MHC I-like molecule CD Id. NKT cells can have either protective or harmful effects due to their ability to produce cytokines that promote either inflammation or immune tolerance. Also included are "gamma delta T cells (γδ T cells)," which refer to a specialized population of a small subset of T cells that have a distinct TCR on their surface. Unlike the majority of T cells, whose TCR is composed of two glycoprotein chains called α and β-TCR chains, the TCR in γδ T cells is composed of γ and δ chains. γδ T cells can play a role in immune surveillance and immune regulation, are an important source of IL-17, and are potent CD8 + It has been found that T cells induce cytotoxic T cell responses. Also included are "regulatory T cells" or "Tregs," which refer to T cells that suppress abnormal or excessive immune responses and play a role in immune tolerance. Tregs are typically CD4+ cells that express the transcription factor Foxp3. + T cells and IL-10-producing CD4 + It may also include transcription factor Foxp3-negative regulatory T cells, which are T cells.

[0071] "Natural killer cells" or "NK cells" refer to differentiated lymphocytes with a CD16+CD56+ and / or CD57+TCR- phenotype. NKs are characterized by their ability to bind to and kill cells that fail to express "self" MHC / HLA antigens through the activation of specific cytolytic enzymes, to kill tumor cells or other diseased cells that express ligands for NK-activating receptors, and to release protein molecules called cytokines that stimulate or inhibit the immune response.

[0072] "About" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which will depend in part on the limitations of how the value is measured or determined, i.e., the measurement system. Unless expressly stated otherwise in the examples or elsewhere in the specification in the context of a particular assay, result, or embodiment, "about" means within one standard deviation or a range of up to 5%, whichever is greater, according to practice in the art.

[0073] An "antigen presenting cell" (APC) refers to any cell that presents antigens on its surface in association with major histocompatibility complex molecules, either MHC class I or MHC class II molecules, or both.

[0074] "Prime-boost" or "prime-boost regimen" refers to a method of treating a subject that involves priming a T cell response with a first vaccine, followed by boosting the immune response with a second vaccine. The first and second vaccines are typically different. These prime-boost immunizations elicit a greater and broader immune response than can be achieved by priming and boosting with the same vaccine. The priming step initiates memory cells, and the boosting step expands the memory response. Boosting can be performed one or more times.

[0075] A "facilitating element" refers to any polynucleotide or polypeptide element operably linked to a polynucleotide or polypeptide, including promoters, enhancers, polyadenylation signals, stop codons, protein tags such as histidine tags, etc. Facilitating elements, as used herein, include regulatory elements.

[0076] "Different" in the context of polypeptide or polynucleotide sequences refers to polypeptide or polynucleotide sequences that are not identical.

[0077] Material composition The present disclosure relates to ovarian cancer neoantigens, polynucleotides encoding same, vectors, host cells, vaccines comprising neoantigens or polynucleotides encoding the neoantigens, proteinaceous molecules that bind to ovarian neoantigens, and methods of making and using same. The present disclosure also provides vaccines comprising the ovarian cancer neoantigens of the present disclosure that are prevalent in the ovarian cancer patient population, thereby providing a pan-vaccine that may be useful in treating a broad population of patients diagnosed with various stages of ovarian cancer, such as localized or metastatic ovarian cancer.

[0078] Cancer cells produce neoantigens that arise from genomic alterations and aberrant transcriptional programs. Neoantigen burden in patients is associated with response to immunotherapy (Snyder et al., N Engl J Med. 2014 Dec 4;371(23):2189-2199; Le et al., N Engl J Med. 2015 Jun 25;372(26):2509-20; Rizvi et al., Science. 2015 Apr 3;348(6230):124-8; Van Allen et al., Science. 2015 Oct 9;350(6257):207-211). The present disclosure is based, at least in part, on the identification of ovarian cancer neoantigens that are common to ovarian cancer patients and, therefore, can be utilized to develop therapeutics that are acceptable for treating a wide range of ovarian cancer patients. One or more neoantigens or polynucleotides encoding the neoantigens of the present disclosure can also be used for diagnostic or prognostic purposes.

[0079] Polypeptides Disclosed herein are polypeptides comprising ovarian cancer neo-antigen sequences that are capable of eliciting an immune response in a subject.

[0080] In some embodiments, the present disclosure provides the nucleic acids of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 200, 201, 202, 203, 204, 205, 206, 207, 20 19, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 2 21, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 3 23, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, or a fragment thereof. In some embodiments, the isolated polypeptide may comprise at least two or more ovarian cancer neo-antigen sequences.

[0081] In some embodiments, the present disclosure provides the nucleic acids of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 16 21, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 2 25, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 3 29, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, and 405, and fragments thereof. In some embodiments, the two or more polypeptides disclosed herein can be present in tandem repeats in any order.

[0082] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:1, or a fragment thereof.

[0083] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 3, or a fragment thereof.

[0084] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 5, or a fragment thereof.

[0085] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 7, or a fragment thereof.

[0086] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 9, or a fragment thereof.

[0087] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 11, or a fragment thereof.

[0088] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 13, or a fragment thereof.

[0089] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 15, or a fragment thereof.

[0090] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 17, or a fragment thereof.

[0091] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 19, or a fragment thereof.

[0092] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 21, or a fragment thereof.

[0093] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 23, or a fragment thereof.

[0094] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 25, or a fragment thereof.

[0095] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 27, or a fragment thereof.

[0096] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:29, or a fragment thereof.

[0097] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 31, or a fragment thereof.

[0098] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 33, or a fragment thereof.

[0099] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 35, or a fragment thereof.

[0100] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 37, or a fragment thereof.

[0101] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 39, or a fragment thereof.

[0102] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 41, or a fragment thereof.

[0103] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 43, or a fragment thereof.

[0104] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 45, or a fragment thereof.

[0105] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 47, or a fragment thereof.

[0106] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 49, or a fragment thereof.

[0107] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 51, or a fragment thereof.

[0108] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 53, or a fragment thereof.

[0109] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 55, or a fragment thereof.

[0110] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 57, or a fragment thereof.

[0111] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 59, or a fragment thereof.

[0112] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 61, or a fragment thereof.

[0113] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 63, or a fragment thereof.

[0114] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 65, or a fragment thereof.

[0115] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 67, or a fragment thereof.

[0116] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 69, or a fragment thereof.

[0117] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 71, or a fragment thereof.

[0118] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 73, or a fragment thereof.

[0119] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 75, or a fragment thereof.

[0120] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 77, or a fragment thereof.

[0121] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 79, or a fragment thereof.

[0122] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 81, or a fragment thereof.

[0123] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 83, or a fragment thereof.

[0124] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 85, or a fragment thereof.

[0125] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 87, or a fragment thereof.

[0126] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 89, or a fragment thereof.

[0127] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 91, or a fragment thereof.

[0128] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 93, or a fragment thereof.

[0129] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 95, or a fragment thereof.

[0130] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 97, or a fragment thereof.

[0131] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 99, or a fragment thereof.

[0132] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 101, or a fragment thereof.

[0133] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 103, or a fragment thereof.

[0134] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 105, or a fragment thereof.

[0135] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 107, or a fragment thereof.

[0136] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 109, or a fragment thereof.

[0137] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 111, or a fragment thereof.

[0138] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 113, or a fragment thereof.

[0139] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 115, or a fragment thereof.

[0140] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 117, or a fragment thereof.

[0141] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 119, or a fragment thereof.

[0142] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 121, or a fragment thereof.

[0143] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 123, or a fragment thereof.

[0144] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 125, or a fragment thereof.

[0145] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 127, or a fragment thereof.

[0146] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 129, or a fragment thereof.

[0147] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 131, or a fragment thereof.

[0148] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 133, or a fragment thereof.

[0149] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 135, or a fragment thereof.

[0150] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 137, or a fragment thereof.

[0151] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 139, or a fragment thereof.

[0152] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 141, or a fragment thereof.

[0153] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 143, or a fragment thereof.

[0154] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 145, or a fragment thereof.

[0155] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 147, or a fragment thereof.

[0156] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 149, or a fragment thereof.

[0157] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 151, or a fragment thereof.

[0158] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 153, or a fragment thereof.

[0159] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 155, or a fragment thereof.

[0160] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 157, or a fragment thereof.

[0161] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 159, or a fragment thereof.

[0162] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 161, or a fragment thereof.

[0163] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 163, or a fragment thereof.

[0164] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 165, or a fragment thereof.

[0165] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 167, or a fragment thereof.

[0166] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 169, or a fragment thereof.

[0167] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 171, or a fragment thereof.

[0168] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 173, or a fragment thereof.

[0169] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 175, or a fragment thereof.

[0170] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 177, or a fragment thereof.

[0171] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 179, or a fragment thereof.

[0172] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 181, or a fragment thereof.

[0173] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 183, or a fragment thereof.

[0174] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 185, or a fragment thereof.

[0175] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 187, or a fragment thereof.

[0176] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 189, or a fragment thereof.

[0177] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 191, or a fragment thereof.

[0178] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 193, or a fragment thereof.

[0179] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 195, or a fragment thereof.

[0180] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 197, or a fragment thereof.

[0181] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 199, or a fragment thereof.

[0182] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 201, or a fragment thereof.

[0183] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 203, or a fragment thereof.

[0184] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 205, or a fragment thereof.

[0185] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 207, or a fragment thereof.

[0186] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 209, or a fragment thereof.

[0187] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 211, or a fragment thereof.

[0188] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 213, or a fragment thereof.

[0189] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 215, or a fragment thereof.

[0190] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 217, or a fragment thereof.

[0191] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 219, or a fragment thereof.

[0192] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 221, or a fragment thereof.

[0193] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 223, or a fragment thereof.

[0194] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 225, or a fragment thereof.

[0195] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 227, or a fragment thereof.

[0196] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 229, or a fragment thereof.

[0197] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 231, or a fragment thereof.

[0198] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 233, or a fragment thereof.

[0199] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 235, or a fragment thereof.

[0200] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 237, or a fragment thereof.

[0201] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 239, or a fragment thereof.

[0202] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 241, or a fragment thereof.

[0203] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 243, or a fragment thereof.

[0204] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 245, or a fragment thereof.

[0205] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 247, or a fragment thereof.

[0206] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 249, or a fragment thereof.

[0207] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 251, or a fragment thereof.

[0208] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 253, or a fragment thereof.

[0209] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 255, or a fragment thereof.

[0210] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 257, or a fragment thereof.

[0211] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 259, or a fragment thereof.

[0212] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 261, or a fragment thereof.

[0213] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 263, or a fragment thereof.

[0214] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 265, or a fragment thereof.

[0215] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 267, or a fragment thereof.

[0216] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 269, or a fragment thereof.

[0217] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 271, or a fragment thereof.

[0218] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 273, or a fragment thereof.

[0219] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 275, or a fragment thereof.

[0220] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 277, or a fragment thereof.

[0221] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 279, or a fragment thereof.

[0222] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 281, or a fragment thereof.

[0223] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 283, or a fragment thereof.

[0224] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 285, or a fragment thereof.

[0225] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 287, or a fragment thereof.

[0226] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 289, or a fragment thereof.

[0227] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 291, or a fragment thereof.

[0228] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 293, or a fragment thereof.

[0229] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 295, or a fragment thereof.

[0230] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 297, or a fragment thereof.

[0231] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 299, or a fragment thereof.

[0232] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 301, or a fragment thereof.

[0233] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 303, or a fragment thereof.

[0234] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 305, or a fragment thereof.

[0235] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 307, or a fragment thereof.

[0236] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 309, or a fragment thereof.

[0237] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 311, or a fragment thereof.

[0238] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 313, or a fragment thereof.

[0239] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 315, or a fragment thereof.

[0240] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 317, or a fragment thereof.

[0241] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 319, or a fragment thereof.

[0242] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 321, or a fragment thereof.

[0243] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 323, or a fragment thereof.

[0244] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 325, or a fragment thereof.

[0245] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 327, or a fragment thereof.

[0246] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 329, or a fragment thereof.

[0247] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 331, or a fragment thereof.

[0248] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 333, or a fragment thereof.

[0249] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 335, or a fragment thereof.

[0250] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 337, or a fragment thereof.

[0251] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 339, or a fragment thereof.

[0252] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 341, or a fragment thereof.

[0253] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 343, or a fragment thereof.

[0254] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 345, or a fragment thereof.

[0255] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 347, or a fragment thereof.

[0256] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 349, or a fragment thereof.

[0257] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 351, or a fragment thereof.

[0258] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 353, or a fragment thereof.

[0259] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 355, or a fragment thereof.

[0260] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 357, or a fragment thereof.

[0261] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 359, or a fragment thereof.

[0262] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 361, or a fragment thereof.

[0263] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 363, or a fragment thereof.

[0264] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 365, or a fragment thereof.

[0265] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 367, or a fragment thereof.

[0266] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 369, or a fragment thereof.

[0267] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 371, or a fragment thereof.

[0268] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 373, or a fragment thereof.

[0269] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 375, or a fragment thereof.

[0270] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 377, or a fragment thereof.

[0271] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 379, or a fragment thereof.

[0272] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 381, or a fragment thereof.

[0273] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 383, or a fragment thereof.

[0274] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 385, or a fragment thereof.

[0275] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 387, or a fragment thereof.

[0276] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 389, or a fragment thereof.

[0277] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 391, or a fragment thereof.

[0278] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 393, or a fragment thereof.

[0279] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 395, or a fragment thereof.

[0280] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 397, or a fragment thereof.

[0281] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 399, or a fragment thereof.

[0282] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 401, or a fragment thereof.

[0283] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 403, or a fragment thereof.

[0284] The present disclosure also provides an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 405, or a fragment thereof.

[0285] In some embodiments, the fragment comprises between about 6 and 24 amino acids in length.

[0286] In some embodiments, the fragments comprise at least 6 amino acids. In some embodiments, the fragments comprise at least 7 amino acids. In some embodiments, the fragments comprise at least 8 amino acids. In some embodiments, the fragments comprise at least 9 amino acids. In some embodiments, the fragments comprise at least 10 amino acids. In some embodiments, the fragments comprise at least 11 amino acids. In some embodiments, the fragments comprise at least 12 amino acids. In some embodiments, the fragments comprise at least 13 amino acids. In some embodiments, the fragments comprise at least 14 amino acids. In some embodiments, the fragments comprise at least 15 amino acids. In some embodiments, the fragments comprise at least 16 amino acids. In some embodiments, the fragments comprise at least 17 amino acids. In some embodiments, the fragments comprise at least 18 amino acids. In some embodiments, the fragments comprise at least 19 amino acids. In some embodiments, the fragments comprise at least 20 amino acids. In some embodiments, the fragments comprise at least 21 amino acids. In some embodiments, the fragments comprise at least 22 amino acids. In some embodiments, the fragments comprise at least 23 amino acids. In some embodiments, the fragments comprise at least 24 amino acids. In some embodiments, the fragments comprise at least 25 amino acids. In some embodiments, the fragments comprise about 6 amino acids. In some embodiments, the fragments comprise about 7 amino acids. In some embodiments, the fragments comprise about 8 amino acids. In some embodiments, the fragments comprise about 9 amino acids. In some embodiments, the fragments comprise about 10 amino acids. In some embodiments, the fragments comprise about 11 amino acids. In some embodiments, the fragments comprise about 12 amino acids. In some embodiments, the fragments comprise about 13 amino acids. In some embodiments, the fragments comprise about 14 amino acids. In some embodiments, the fragments comprise about 15 amino acids. In some embodiments, the fragments comprise about 16 amino acids. In some embodiments, the fragments comprise about 17 amino acids. In some embodiments, the fragments comprise about 18 amino acids. In some embodiments, the fragments comprise about 19 amino acids.In some embodiments, the fragments comprise about 20 amino acids. In some embodiments, the fragments comprise about 21 amino acids. In some embodiments, the fragments comprise about 22 amino acids. In some embodiments, the fragments comprise about 23 amino acids. In some embodiments, the fragments comprise about 24 amino acids. In some embodiments, the fragments comprise about 25 amino acids. In some embodiments, the fragments comprise about 6-25 amino acids. In some embodiments, the fragments comprise about 7-25 amino acids. In some embodiments, the fragments comprise about 8-25 amino acids. In some embodiments, the fragments comprise about 8-24 amino acids. In some embodiments, the fragments comprise about 8-23 amino acids. In some embodiments, the fragments comprise about 8-22 amino acids. In some embodiments, the fragments comprise about 8-21 amino acids. In some embodiments, the fragments comprise about 8-20 amino acids. In some embodiments, the fragments comprise about 8-19 amino acids. In some embodiments, the fragments comprise about 8-18 amino acids. In some embodiments, the fragments comprise about 8-17 amino acids. In some embodiments, the fragments comprise about 8-16 amino acids. In some embodiments, the fragment comprises about 8-15 amino acids. In some embodiments, the fragment comprises about 8-14 amino acids. In some embodiments, the fragment comprises about 9-14 amino acids. In some embodiments, the fragment comprises about 9-13 amino acids. In some embodiments, the fragment comprises about 9-12 amino acids. In some embodiments, the fragment comprises about 9-11 amino acids. In some embodiments, the fragment comprises about 9-10 amino acids.

[0287] In some embodiments, the fragment is an immunogenic fragment.

[0288] Immunogenic fragments are generally peptides that activate T cells, e.g., those that induce cytotoxic T cells when presented on MHC. Methods for assessing T cell activation and / or induction of cytotoxic T lymphocytes are well known. In an exemplary assay, PBMCs isolated from ovarian cancer patients are cultured in vitro in the presence of a test neoantigen or a fragment thereof and IL-25. The cultures may be periodically supplemented with IL-15 and IL-2 and cultured for an additional 12 days. On day 12, the cultures are restimulated with the test neoantigen or a fragment thereof, and the following day, IFNγ levels are increased compared to control cultures. + TNAα + CD8 + By measuring the percentage of cells, T cell activation can be assessed.

[0289] The polypeptides and heterologous polypeptides of the present disclosure are useful for generating recombinant viruses, cells, and vaccines of the present disclosure, as well as proteinaceous molecules that specifically bind to one or more ovarian neo-antigens of the present disclosure, or may be used directly as therapeutic agents by delivery to a subject with ovarian cancer using a variety of techniques. Two or more neo-antigens (e.g., polypeptides) may be incorporated into a vaccine in any order using standard cloning methods.

[0290] Through the validation process, SEQ ID NOs: 1, 3, 5, 11, 15, 17, 19, 21, 25, 29, 31, 33, 39, 43, 45, 49, 53, 59, 63, 65, 67, 81, 85, 87, 89, 91, 95, 97, 111, 113, 115, 119, 123, 127, 129, 145, 177, 179, 181, 183, 185, 187, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 215, 219, 221, 223, 229, 233, Ninety-five neoantigen polypeptides have been identified as particularly useful for inclusion in ovarian cancer vaccines based on their expression profiles, prevalence, and in vitro immunogenicity: 235, 237, 239, 241, 243, 245, 247, 251, 255, 257, 259, 261, 263, 267, 271, 279, 281, 285, 293, 295, 297, 301, 303, 305, 307, 309, 319, 323, 325, 337, 339, 343, 345, 349, 371, and 375. It is anticipated that any combination of two or more of the 95 neoantigens can be utilized to generate an ovarian cancer vaccine that can be delivered to a subject using any available delivery vehicle and in any available form, e.g., peptide, DNA, RNA, replicon, or viral delivery. Using standard cloning methods, two or more neo-antigens (e.g., polypeptides) may be incorporated into the vaccine in any order.

[0291] Two or more of the 95 polypeptides may be assembled into a heterologous polynucleotide encoding the heterologous polypeptide in any order, and the order of the polypeptides may vary among various delivery options. Generally, assembly of the polypeptides in a particular order may be based on generating a minimum number of junctional epitopes using known algorithms.

[0292] In some embodiments, the present disclosure provides the nucleic acids of SEQ ID NOs: 1, 3, 5, 11, 15, 17, 19, 21, 25, 29, 31, 33, 39, 43, 45, 49, 53, 59, 63, 65, 67, 81, 85, 87, 89, 91, 95, 97, 111, 113, 115, 119, 123, 127, 129, 145, 177, 179, 181, 183, 185, 187, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 215, 219, 221, 223, 229, 233, 235, 237, 239, 241, 243, 245, 247, 251, 255, 257, 259, 261, 263, 267, 271, 279, 281, 285, 293, 295, 297, 301, 303, 305, 307, 309, 319, 323, 325, 337, 339, 343, 345, 349, 371, or 375, or fragments thereof.

[0293] The present disclosure also relates to SEQ ID NOs: 1, 3, 5, 11, 15, 17, 19, 21, 25, 29, 31, 33, 39, 43, 45, 49, 53, 59, 63, 65, 67, 81, 85, 87, 89, 91, 95, 97, 111, 113, 115, 119, 123, 127, 129, 145, 177, 179, 181, 183, 185, 187, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 215, 219, In some embodiments, the polypeptide comprises two or more tandem repeats of 221, 223, 229, 233, 235, 237, 239, 241, 243, 245, 247, 251, 255, 257, 259, 261, 263, 267, 271, 279, 281, 285, 293, 295, 297, 301, 303, 305, 307, 309, 319, 323, 325, 337, 339, 343, 345, 349, 371, or 375, or fragments thereof. In some embodiments, the polypeptide comprises 2, 3, 4, 5, or more than 5 repeats of a polypeptide of the present disclosure.

[0294] In some embodiments, the polypeptide is head-to-tail joined.

[0295] In some embodiments, the polypeptides may be separated by a linker.

[0296] Exemplary linker sequences include AAY, RR, DPP, HHAA, HHA, HHL, RKSYL, RKSY, SSL, or REKR. In some embodiments, the linkers disclosed herein may contain a protease cleavage site such that the heterologous polypeptide can be cleaved into peptide fragments comprising the neo-antigen sequence in vivo in a subject, resulting in an improved immune response.

[0297] In some embodiments, the polypeptides are joined directly to each other without a linker, without including a linker.

[0298] In some embodiments, the polypeptides of the present disclosure may further comprise a leader sequence or T-cell enhancer sequence (TCE) at the N-terminus. Leader sequences can increase expression and / or increase immunological responses. Exemplary leader sequences include T 2 Examples of such leader sequences include the alpha chain of the lymphocyte TCR receptor (HAVT20) (MACPGFLWALVISTC LEFSMA; SEQ ID NO: 419), the ubiquitin signal sequence (Ubiq) (MQIFVKTLTGKTITLEVEP SDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGVR; SEQ ID NO: 420), or a T cell enhancer (TCE) sequence (MGQKEQIHTLQKNSERMSKQLTRSSQAV; SEQ ID NO: 421), such as a 28-aa-long peptide fragment from the mandarin fish invariant chain. It is believed that leader sequences may be useful in increasing the immune response to the epitopes disclosed herein.

[0299] Polynucleotides The present disclosure also provides polynucleotides that encode any of the polypeptides disclosed herein.

[0300] In some embodiments, the present disclosure provides the nucleic acids of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 16 9, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221 , 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323,

[0023] In one embodiment, an isolated polynucleotide encoding a polypeptide of 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, or a fragment thereof, is provided.

[0301] The present disclosure also provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125 , 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229 , 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 332 3, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, or a fragment thereof, are provided.

[0302] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 17 24, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326 , 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, or 406, or a fragment thereof.

[0303] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126 , 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 380, 382, ​​384, 386, 388, 390, 36, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, or 406, or a fragment thereof, are provided.

[0304] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 18 26, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332 , 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, and 406, and fragments thereof.

[0305] The present disclosure also provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 200, 201, 202, 203, 27, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231 , 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, and 405, and fragments thereof.

[0306] In some embodiments, the fragments comprise at least 18 nucleotides. In some embodiments, the fragments comprise at least 21 nucleotides. In some embodiments, the fragments comprise at least 24 nucleotides. In some embodiments, the fragments comprise at least 27 nucleotides. In some embodiments, the fragments comprise at least 30 nucleotides. In some embodiments, the fragments comprise at least 33 nucleotides. In some embodiments, the fragments comprise at least 36 nucleotides. In some embodiments, the fragments comprise at least 39 nucleotides. In some embodiments, the fragments comprise at least 42 nucleotides. In some embodiments, the fragments comprise at least 45 nucleotides. In some embodiments, the fragments comprise at least 48 nucleotides. In some embodiments, the fragments comprise at least 51 nucleotides. In some embodiments, the fragments comprise at least 54 nucleotides. In some embodiments, the fragments comprise at least 57 nucleotides. In some embodiments, the fragments comprise at least 60 nucleotides. In some embodiments, the fragments comprise at least 63 nucleotides. In some embodiments, the fragments comprise at least 66 nucleotides. In some embodiments, the fragments comprise at least 69 nucleotides. In some embodiments, the fragments comprise at least 72 nucleotides. In some embodiments, the fragments comprise at least 75 nucleotides. In some embodiments, the fragments comprise about 18 nucleotides. In some embodiments, the fragments comprise about 21 nucleotides. In some embodiments, the fragments comprise about 24 nucleotides. In some embodiments, the fragments comprise about 27 nucleotides. In some embodiments, the fragments comprise about 30 nucleotides. In some embodiments, the fragments comprise about 33 nucleotides. In some embodiments, the fragments comprise about 36 nucleotides. In some embodiments, the fragments comprise about 39 nucleotides. In some embodiments, the fragments comprise about 42 nucleotides. In some embodiments, the fragments comprise about 45 nucleotides. In some embodiments, the fragments comprise about 48 nucleotides.In some embodiments, the fragments comprise about 51 nucleotides. In some embodiments, the fragments comprise about 54 nucleotides. In some embodiments, the fragments comprise about 57 nucleotides. In some embodiments, the fragments comprise about 60 nucleotides. In some embodiments, the fragments comprise about 63 nucleotides. In some embodiments, the fragments comprise about 66 nucleotides. In some embodiments, the fragments comprise about 69 nucleotides. In some embodiments, the fragments comprise about 72 nucleotides. In some embodiments, the fragments comprise about 75 nucleotides. In some embodiments, the fragments comprise about 18-75 nucleotides. In some embodiments, the fragments comprise about 21-75 nucleotides. In some embodiments, the fragments comprise about 24-75 nucleotides. In some embodiments, the fragments comprise about 24-72 nucleotides. In some embodiments, the fragments comprise about 24-69 nucleotides. In some embodiments, the fragments comprise about 24-66 nucleotides. In some embodiments, the fragments comprise about 24-63 nucleotides. In some embodiments, the fragments comprise about 24-60 nucleotides. In some embodiments, the fragments comprise about 24-57 nucleotides. In some embodiments, the fragment comprises about 24-54 nucleotides. In some embodiments, the fragment comprises about 24-51 nucleotides. In some embodiments, the fragment comprises about 24-48 nucleotides. In some embodiments, the fragment comprises about 24-45 nucleotides. In some embodiments, the fragment comprises about 24-42 nucleotides. In some embodiments, the fragment comprises about 27-42 nucleotides. In some embodiments, the fragment comprises about 27-39 nucleotides. In some embodiments, the fragment comprises about 27-36 nucleotides. In some embodiments, the fragment comprises about 27-33 nucleotides. In some embodiments, the fragment comprises about 27-30 nucleotides.

[0307] The polynucleotides and heterologous polynucleotides of the present disclosure encode ovarian neoantigens and heterologous polypeptides comprising two or more ovarian neoantigens described herein. The polynucleotides and heterologous polynucleotides of the present disclosure are useful for producing the polypeptides, heterologous polypeptides, vectors, recombinant viruses, cells, and vaccines of the present disclosure. The polynucleotides and heterologous polynucleotides of the present disclosure can be utilized as therapeutic agents by delivery to a subject with ovarian cancer using a variety of techniques, including viral vectors described herein or other delivery techniques also described herein.

[0308] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 1, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 1, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 2, or a fragment thereof.

[0309] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 3, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 3, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 4, or a fragment thereof.

[0310] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 5, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 5, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 6, or a fragment thereof.

[0311] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 7, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 7, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 8, or a fragment thereof.

[0312] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 9, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 9, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 10, or a fragment thereof.

[0313] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 11, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 11, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 12, or a fragment thereof.

[0314] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 13, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 13, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 14, or a fragment thereof.

[0315] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 15, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 15, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 16, or a fragment thereof.

[0316] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 17, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 17, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 18, or a fragment thereof.

[0317] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 19, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 19, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 20, or a fragment thereof.

[0318] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 21, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 21, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 22, or a fragment thereof.

[0319] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 23, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 23, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 24, or a fragment thereof.

[0320] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 25, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 25, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 26, or a fragment thereof.

[0321] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 27, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 27, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 28, or a fragment thereof.

[0322] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 29, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 29, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 30, or a fragment thereof.

[0323] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 31, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 31, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 32, or a fragment thereof.

[0324] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 33, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 33, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 34, or a fragment thereof.

[0325] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 35, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 35, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 36, or a fragment thereof.

[0326] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 37, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 37, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 38, or a fragment thereof.

[0327] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 39, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 39, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 40, or a fragment thereof.

[0328] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 41, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 41, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 42, or a fragment thereof.

[0329] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 43, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 43, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 44, or a fragment thereof.

[0330] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 45, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 45, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 46, or a fragment thereof.

[0331] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 47, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 47, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 48, or a fragment thereof.

[0332] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 49, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 49, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 50, or a fragment thereof.

[0333] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 51, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 51, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 52, or a fragment thereof.

[0334] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 53, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 53, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 54, or a fragment thereof.

[0335] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 55, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 55, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 56, or a fragment thereof.

[0336] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 57, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 57, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 58, or a fragment thereof.

[0337] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 59, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 59, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 60, or a fragment thereof.

[0338] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 61, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 61, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 62, or a fragment thereof.

[0339] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 63, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 63, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 64, or a fragment thereof.

[0340] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 65, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 65, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 66, or a fragment thereof.

[0341] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 67, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 67, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 68, or a fragment thereof.

[0342] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 69, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 69, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 70, or a fragment thereof.

[0343] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 71, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 71, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 72, or a fragment thereof.

[0344] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 73, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 73, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 74, or a fragment thereof.

[0345] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 75, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 75, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 76, or a fragment thereof.

[0346] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 77, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 77, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 78, or a fragment thereof.

[0347] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 79, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 79, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 80, or a fragment thereof.

[0348] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 81, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 81, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 82, or a fragment thereof.

[0349] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 83, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 83, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 84, or a fragment thereof.

[0350] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 85, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 85, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 86, or a fragment thereof.

[0351] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 87, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 87, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 88, or a fragment thereof.

[0352] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 89, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 89, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 90, or a fragment thereof.

[0353] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 91, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 91, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 92, or a fragment thereof.

[0354] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 93, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 93, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 94, or a fragment thereof.

[0355] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 95, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 95, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 96, or a fragment thereof.

[0356] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 97, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 97, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 98, or a fragment thereof.

[0357] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 99, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 99, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 100, or a fragment thereof.

[0358] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 101, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 101, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 102, or a fragment thereof.

[0359] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 103, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 103, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 104, or a fragment thereof.

[0360] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 105, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 105, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 106, or a fragment thereof.

[0361] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 107, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 107, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 108, or a fragment thereof.

[0362] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 109, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 109, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 110, or a fragment thereof.

[0363] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 111, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 111, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 112, or a fragment thereof.

[0364] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 113, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 113, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 114, or a fragment thereof.

[0365] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 115, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 115, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 116, or a fragment thereof.

[0366] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 117, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 117, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 118, or a fragment thereof.

[0367] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 119, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 119, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 120, or a fragment thereof.

[0368] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 121, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 121, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 122, or a fragment thereof.

[0369] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 123, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 123, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 124, or a fragment thereof.

[0370] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 125, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 125, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 126, or a fragment thereof.

[0371] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 127, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 127, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 128, or a fragment thereof.

[0372] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 129, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 129, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 130, or a fragment thereof.

[0373] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 131, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 131, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 132, or a fragment thereof.

[0374] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 133, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 133, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 134, or a fragment thereof.

[0375] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 135, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 135, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 136, or a fragment thereof.

[0376] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 137, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 137, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 138, or a fragment thereof.

[0377] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 139, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 139, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 140, or a fragment thereof.

[0378] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 141, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 141, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 142, or a fragment thereof.

[0379] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 143, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 143, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 144, or a fragment thereof.

[0380] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 145, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 145, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 146, or a fragment thereof.

[0381] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 147, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 147, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 148, or a fragment thereof.

[0382] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 149, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 149, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 150, or a fragment thereof.

[0383] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 151, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 151, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 152, or a fragment thereof.

[0384] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 153, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 153, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 154, or a fragment thereof.

[0385] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 155, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 155, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 156, or a fragment thereof.

[0386] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 157, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 157, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 158, or a fragment thereof.

[0387] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 159, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 159, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 160, or a fragment thereof.

[0388] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 161, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 161, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 162, or a fragment thereof.

[0389] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 163, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 163, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 164, or a fragment thereof.

[0390] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 165, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 165, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 166, or a fragment thereof.

[0391] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 167, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 167, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 168, or a fragment thereof.

[0392] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 169, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 169, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 170, or a fragment thereof.

[0393] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 171, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 171, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 172, or a fragment thereof.

[0394] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 173, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 173, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 174, or a fragment thereof.

[0395] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 175, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 175, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 176, or a fragment thereof.

[0396] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 177, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 177, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 178, or a fragment thereof.

[0397] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 179, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 179, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 180, or a fragment thereof.

[0398] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 181, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 181, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 182, or a fragment thereof.

[0399] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 183, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 183, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 184, or a fragment thereof.

[0400] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 185, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 185, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 186, or a fragment thereof.

[0401] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 187, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 187, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 188, or a fragment thereof.

[0402] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 189, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 189, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 190, or a fragment thereof.

[0403] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 191, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 191, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 192, or a fragment thereof.

[0404] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 193, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 193, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 194, or a fragment thereof.

[0405] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 195, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 195, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 196, or a fragment thereof.

[0406] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 197, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 197, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 198, or a fragment thereof.

[0407] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 199, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 199, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 200, or a fragment thereof.

[0408] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 201, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 201, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 202, or a fragment thereof.

[0409] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 203, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 203, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 204, or a fragment thereof.

[0410] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 205, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 205, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 206, or a fragment thereof.

[0411] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 207, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 207, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 208, or a fragment thereof.

[0412] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 209, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 209, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 210, or a fragment thereof.

[0413] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 211, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 211, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 212, or a fragment thereof.

[0414] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 213, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 213, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 214, or a fragment thereof.

[0415] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 215, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 215, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 216, or a fragment thereof.

[0416] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 217, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 217, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 218, or a fragment thereof.

[0417] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 219, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 219, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 220, or a fragment thereof.

[0418] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 221, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 221, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 222, or a fragment thereof.

[0419] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 223, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 223, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 224, or a fragment thereof.

[0420] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 225, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 225, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 226, or a fragment thereof.

[0421] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 227, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 227, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 228, or a fragment thereof.

[0422] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 229, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 229, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 230, or a fragment thereof.

[0423] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 231, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 231, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 232, or a fragment thereof.

[0424] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 233, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 233, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 234, or a fragment thereof.

[0425] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 235, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 235, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 236, or a fragment thereof.

[0426] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 237, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 237, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 238, or a fragment thereof.

[0427] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 239, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 239, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 240, or a fragment thereof.

[0428] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 241, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 241, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 242, or a fragment thereof.

[0429] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 243, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 243, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 244, or a fragment thereof.

[0430] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 245, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 245, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 246, or a fragment thereof.

[0431] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 247, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 247, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 248, or a fragment thereof.

[0432] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 249, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 249, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 250, or a fragment thereof.

[0433] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 251, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 251, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 252, or a fragment thereof.

[0434] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 253, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 253, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 254, or a fragment thereof.

[0435] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 255, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 255, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 256, or a fragment thereof.

[0436] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 257, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 257, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 258, or a fragment thereof.

[0437] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 259, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 259, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 260, or a fragment thereof.

[0438] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 261, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 261, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 262, or a fragment thereof.

[0439] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 263, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 263, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 264, or a fragment thereof.

[0440] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 265, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 265, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 266, or a fragment thereof.

[0441] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 267, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 267, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 268, or a fragment thereof.

[0442] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 269, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 269, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 270, or a fragment thereof.

[0443] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 271, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 271, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 272, or a fragment thereof.

[0444] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 273, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 273, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 274, or a fragment thereof.

[0445] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 275, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 275, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 276, or a fragment thereof.

[0446] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 277, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 277, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 278, or a fragment thereof.

[0447] The present disclosure also provides an isolated polynucleotide encoding a polypeptide of SEQ ID NO: 279, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 279, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 280, or a fragment thereof.

[0448] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 281, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 281, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 282, or a fragment thereof.

[0449] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 283, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 283, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 284, or a fragment thereof.

[0450] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 285, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 285, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 286, or a fragment thereof.

[0451] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 287, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 287, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 288, or a fragment thereof.

[0452] The present disclosure also provides an isolated polynucleotide encoding a polypeptide of SEQ ID NO: 289, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 289, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 290, or a fragment thereof.

[0453] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 291, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 291, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 292, or a fragment thereof.

[0454] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 293, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 293, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 294, or a fragment thereof.

[0455] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 295, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 295, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 296, or a fragment thereof.

[0456] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 297, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 297, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 298, or a fragment thereof.

[0457] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 299, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 299, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 300, or a fragment thereof.

[0458] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 301, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 301, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 302, or a fragment thereof.

[0459] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 303, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 303, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 304, or a fragment thereof.

[0460] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 305, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 305, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 306, or a fragment thereof.

[0461] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 307, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 307, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 308, or a fragment thereof.

[0462] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 309, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 309, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 310, or a fragment thereof.

[0463] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 311, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 311, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 312, or a fragment thereof.

[0464] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 313, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 313, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 314, or a fragment thereof.

[0465] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 315, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 315, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 316, or a fragment thereof.

[0466] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 317, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 317, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 318, or a fragment thereof.

[0467] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 319, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 319, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 320, or a fragment thereof.

[0468] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 321, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 321, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 322, or a fragment thereof.

[0469] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 323, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 323, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 324, or a fragment thereof.

[0470] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 325, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 325, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 326, or a fragment thereof.

[0471] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 327, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 327, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 328, or a fragment thereof.

[0472] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 329, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 329, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 330, or a fragment thereof.

[0473] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 331, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 331, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 332, or a fragment thereof.

[0474] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 333, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 333, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 334, or a fragment thereof.

[0475] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 335, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 335, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 336, or a fragment thereof.

[0476] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 337, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 337, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 338, or a fragment thereof.

[0477] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 339, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 339, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 340, or a fragment thereof.

[0478] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 341, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 341, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 342, or a fragment thereof.

[0479] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 343, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 343, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 344, or a fragment thereof.

[0480] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 345, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 345, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 346, or a fragment thereof.

[0481] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 347, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 347, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 348, or a fragment thereof.

[0482] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 349, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 349, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 350, or a fragment thereof.

[0483] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 351, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 351, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 352, or a fragment thereof.

[0484] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 353, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 353, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 354, or a fragment thereof.

[0485] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 355, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 355, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 356, or a fragment thereof.

[0486] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 357, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 357, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 358, or a fragment thereof.

[0487] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 359, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 359, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 360, or a fragment thereof.

[0488] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 361, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 361, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 362, or a fragment thereof.

[0489] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 363, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 363, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 364, or a fragment thereof.

[0490] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 365, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 365, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 366, or a fragment thereof.

[0491] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 367, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 367, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 368, or a fragment thereof.

[0492] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 369, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 369, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 370, or a fragment thereof.

[0493] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 371, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 371, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 372, or a fragment thereof.

[0494] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 373, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 373, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 374, or a fragment thereof.

[0495] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 375, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 375, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 376, or a fragment thereof.

[0496] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 377, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 377, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 378, or a fragment thereof.

[0497] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 379, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 379, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 380, or a fragment thereof.

[0498] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 381, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 381, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 382, ​​or a fragment thereof.

[0499] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 383, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 383, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 384, or a fragment thereof.

[0500] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 385, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 385, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 386, or a fragment thereof.

[0501] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 387, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 387, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 388, or a fragment thereof.

[0502] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 389, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 389, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 390, or a fragment thereof.

[0503] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 391, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 391, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 392, or a fragment thereof.

[0504] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 393, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 393, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 394, or a fragment thereof.

[0505] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 395, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 395, or a fragment thereof, is encoded by the polynucleotide of SEQ ID NO: 396, or a fragment thereof.

[0506] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 397, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 397, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 398, or a fragment thereof.

[0507] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 399, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 399, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 400, or a fragment thereof.

[0508] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 401, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 401, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 402, or a fragment thereof.

[0509] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 403, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 403, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 404, or a fragment thereof.

[0510] The present disclosure also provides an isolated polynucleotide encoding the polypeptide of SEQ ID NO: 405, or a fragment thereof. In some embodiments, the polypeptide of SEQ ID NO: 405, or a fragment thereof, is encoded by a polynucleotide of SEQ ID NO: 406, or a fragment thereof.

[0511] In some embodiments, the heterologous polynucleotide is an in-frame heterologous polynucleotide.

[0512] Polynucleotides may be codon optimized for expression in various hosts using known methods.

[0513] In some embodiments, the isolated heterologous polynucleotide is an in-frame heterologous polynucleotide.

[0514] In some embodiments, the polynucleotide comprises DNA or RNA.

[0515] In some embodiments, the polynucleotide comprises RNA.

[0516] In some embodiments, the RNA is mRNA.

[0517] Variants of the genetically engineered polynucleotides, polypeptides, heterologous polynucleotides, and heterologous polypeptides of the present disclosure and Variants of polynucleotides, polypeptides, heterologous polynucleotides, and heterologous polypeptides, or fragments thereof, are within the scope of the present disclosure. For example, variants may contain one or more substitutions, deletions, or insertions, so long as the variant retains or has improved characteristics (such as immunogenicity or stability) compared to the parent. In some embodiments, the sequence identity between the parent and variant may be about 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%. In some embodiments, variants are generated by conservative substitutions.

[0518] In some embodiments, the identity is about 80%. In some embodiments, the identity is about 85%. In some embodiments, the identity is about 90%. In some embodiments, the identity is about 91%. In some embodiments, the identity is about 91%. In some embodiments, the identity is about 92%. In some embodiments, the identity is about 93%. In some embodiments, the identity is about 94%. In some embodiments, the identity is 94%. In some embodiments, the identity is about 95%. In some embodiments, the identity is about 96%. In some embodiments, the identity is about 97%. In some embodiments, the identity is about 98%. In some embodiments, the identity is about 99%.

[0519] The percent identity between two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps and the length of each gap that must be introduced for optimal alignment of the two sequences (i.e., % identity = number of identical positions / total number of positions × 100). The percent identity between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput Appl Biosci, 4, 11-17 (1988)) as incorporated into the ALIGN program (version 2.0), using a PAM120 weighted residue table with a gap length penalty of 12 and a gap penalty of 4. Additionally, the percent identity between two amino acid sequences can be determined using the algorithm of Needleman and Wunsch (J Mol Biol 48:444-453 (1970)) as incorporated into the GAP program in the GCG software package (available at http: / / www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, gap weights of 16, 14, 12, 10, 8, 6, or 4, and length weights of 1, 2, 3, 4, 5, or 6.

[0520] A variant of a polypeptide or heterologous polypeptide, or a fragment thereof, containing a single amino acid change generally retains the same tertiary structure and antigenicity as the parent. In some cases, the variant may also contain at least one amino acid change that increases the antigenicity of the variant, or increases the binding affinity to TCRs or antibodies, or both. A variant of a polypeptide or heterologous polypeptide may also have improved ability to bind to HLA molecules.

[0521] Variants of the present disclosure can be engineered to contain conservative substitutions, which are defined herein as exchanges within one of the following five groups: Group 1—small aliphatic non-polar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); Group 2—polar negatively charged residues and their amides (Asp, Asn, Glu, Gin); Group 3—polar positively charged residues (His, Arg, Lys); Group 4—large aliphatic non-polar residues (Met, Leu, Lie, Val, Cys); and Group 5—large aromatic residues (Phe, Tyr, Trp).

[0522] Variants of the present disclosure may be engineered to contain less conservative substitutions, e.g., the substitution of one amino acid for another amino acid with similar characteristics but slightly different in size, such as the substitution of an alanine with an isoleucine residue. Variants of the present disclosure may also be engineered to contain more non-conservative substitutions, which may include the substitution of an acidic amino acid for one that is polar, or even basic in character.

[0523] Further substitutions that can be made to create variants of the present disclosure include substitutions that may involve structures other than common L-amino acids. Thus, D-amino acids and non-standard amino acids (i.e., other than the common naturally occurring proteinogenic amino acids) can also be used for substitution purposes to generate variants with enhanced immunogenicity when compared to the parent.

[0524] Where more than one substitution is made resulting in a polypeptide or heterologous polypeptide with substantially equivalent or greater immunogenicity, combinations of these substitutions can be tested to determine whether the combined substitutions have an additive or synergistic effect on the immunogenicity of the variant.

[0525] Amino acid residues that do not substantially contribute to interaction with the TCR can be modified by substituting other amino acids whose incorporation does not substantially affect T cell responsiveness and does not eliminate binding to the relevant MHC. Amino acid residues that do not substantially contribute to interaction with the TCR can also be deleted, so long as they do not substantially affect T cell responsiveness and do not eliminate binding to the relevant MHC.

[0526] Additionally, polypeptides or heterologous polypeptides, or fragments or variants thereof, may be further modified to improve stability and / or binding to MHC molecules to elicit a stronger immune response. Methods for optimizing peptide sequences in this manner are well known in the art and include, for example, the introduction of reverse peptide bonds or non-peptide bonds. In reverse peptide bonds, amino acid residues are not joined by peptide (-CO-NH-) bonds, but rather the peptide bonds are reversed. Such retro-inverso peptidomimetics can be generated using methods known in the art, such as those described in Meziere et al. (1997) (Meziere et al., 1997). This approach involves generating pseudopeptides containing changes involving the backbone rather than the orientation of the side chains. Meziere et al. (Meziere et al., 1997) demonstrate the utility of these pseudopeptides for MHC binding and T helper cell responses. Retro-inverso peptides containing NH-CO bonds instead of CO-NH peptide bonds are much more resistant to proteolysis. Additional non-peptide bonds that may be used can be, for example, -CH2-NH, -CH2S-, -CH2CH2-, -CH=CH-, -COCH2-, -CH(OH)CH2-, and -CH2SO-.

[0527] To enhance peptide stability, bioavailability, and / or affinity, polypeptides of the present disclosure or heterologous polypeptides, or fragments or variants thereof, may be synthesized with additional chemical groups at the amino and / or carboxy termini. For example, hydrophobic groups such as carbobenzoxyl, dansyl, or t-butyloxycarbonyl groups may be added to the amino terminus. Similarly, an acetyl group or a 9-fluorenylmethoxy-carbonyl group may be placed at the amino terminus. Additionally, hydrophobic groups, t-butyloxycarbonyl, or amide groups may be added to the carboxy terminus.

[0528] Additionally, a polypeptide or heterologous polypeptide of the present disclosure, or a fragment or variant thereof, may be synthesized to alter its configuration, for example, to use the D-isomer of one or more of the amino acid residues of the peptide, rather than the usual L-isomer.

[0529] Similarly, a polypeptide or heterologous polypeptide of the present disclosure, or a fragment or variant thereof, may be chemically modified by reacting specific amino acids either before or after synthesis of the polypeptide or heterologous polypeptide of the present disclosure, or a fragment or variant thereof. Examples of such modifications are well known in the art and are summarized, for example, in R. Lundblad, Chemical Reagents for Protein Modification, 3rd ed. CRC Press, 2004 (Lundblad, 2004), which is incorporated herein by reference. Chemical modifications of amino acids include, but are not limited to, modifications by acylation, amidation, pyridoxylation of lysine, reductive alkylation, trinitrobenzylation of amino groups with 2,4,6-trinitrobenzenesulfonic acid (TNBS), amide modification of carboxyl groups and sulfhydryl modification of cysteine ​​to cysteic acid by performic acid oxidation, formation of mercury derivatives, formation of mixed disulfides with other thiol compounds, reaction with maleimide, carboxymethylation with iodoacetic acid or iodoacetamide, and carbamoylation with cyanic acid at alkaline pH. In this regard, those skilled in the art are referred to Chapter 15 of Current Protocols in Protein Science, Eds. Coligan et al. (John Wiley and Sons, NY 1995-2000) (Coligan et al., 1995) for a more extensive methodology for chemically modifying proteins.

[0530] Briefly, for example, modification of arginine residues in proteins is often based on the reaction of vicinal dicarbonyl compounds, such as phenylglyoxal, 2,3-butanedione, and 1,2-cyclohexanedione, to form adducts. Another example is the reaction of methylglyoxal with arginine residues. Cysteine ​​can be modified without simultaneously modifying other nucleophilic sites, such as lysine and histidine. Consequently, numerous reagents are available for modifying cysteine. Websites of companies such as Sigma-Aldrich (http: / / www.sigma-aldrich.com) provide information on specific reagents. Selective reduction of disulfide bonds in proteins is also common. Disulfide bonds can form and be oxidized during thermal treatment of biopharmaceuticals. Woodward's reagent K can also be used to modify specific glutamic acid residues. N-(3-(dimethylamino)propyl)-N'-ethylcarbodiimide can be used to form intramolecular crosslinks between lysine and glutamic acid residues. For example, diethylpyrocarbonate is a reagent for modifying histidyl residues in proteins. Histidine can also be modified using 4-hydroxy-2-nonenal. Reactions of lysine residues and other α-amino groups are useful, for example, for attaching peptides to surfaces or crosslinking proteins / peptides. Lysine is the attachment site for poly(ethylene)glycol and the primary site of modification in protein glycosylation. Methionine residues in proteins can be modified with, for example, iodoacetamide, bromoethylamine, and chloramine T. Tetranitromethane and N-acetylimidazole can be used to modify tyrosine residues. Crosslinking via the formation of dityrosine can be achieved with hydrogen peroxide / copper ions. Recent studies on tryptophan modification have used N-bromosuccinimide, 2-hydroxy-5-nitrobenzyl bromide, or 3-bromo-3-methyl-2-(2-nitrophenylmercapto)-3H-indole (BPNS-skatole).Successful modification of therapeutic proteins and peptides with PEG is often associated with increased circulatory half-life, while crosslinking of proteins with glutaraldehyde, polyethylene glycol diacrylate, and formaldehyde is used to prepare hydrogels. Chemical modification of allergens for immunotherapy is often achieved by carbamination with potassium cyanate.

[0531] The present disclosure provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 33, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351 , 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405.

[0532] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132 , 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 353 54, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, or 406.

[0533] The present disclosure also provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 200, 201, 202, 203, 27, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231 , 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335,

[0013] Provided is an isolated polypeptide comprising the amino acid sequence of 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, and fragments thereof, wherein the polypeptide comprises one or more inverted peptide bonds.

[0534] In some embodiments, the reverse peptide bond comprises an NH—CO bond.

[0535] In some embodiments, the reverse peptide bond comprises a —CH 2 —NH, —CH 2 S—, —CH 2 CH 2 —, —CH═CH—, —COCH 2 —, —CH(OH)CH 2 —, or —CH 2 SO— bond.

[0536] The present disclosure also relates to SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172 5, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 33 391, 393, 395, 397, 399, 401, 403, or 405, wherein the polypeptide comprises one or more chemical modifications.

[0537] In some embodiments, the one or more chemical modifications include carbobenzoxyl, dansyl, t-butyloxycarbonyl, 9-fluorenylmethoxy-carbonyl, or D-isomer modifications of amino acids.

[0538] Methods for producing the disclosed polynucleotides and polypeptides The polynucleotides or variants of the present disclosure may be in the form of RNA or in the form of DNA, obtained by cloning or produced synthetically. The DNA may be double-stranded or single-stranded.

[0539] Methods for producing the polynucleotides and heterologous polynucleotides or variants of the present disclosure are known in the art and include chemical synthesis, enzymatic synthesis (e.g., in vitro transcription), enzymatic or chemical cleavage of longer precursors, chemical synthesis of smaller fragments of the polynucleotide followed by ligation of the fragments, or known PCR methods. The synthesized polynucleotide sequence can be designed with appropriate codons for the desired amino acid sequence. Generally, preferred codons may be selected for the intended host in which the sequence will be used for expression.

[0540] Methods for producing the polypeptides and heterologous polypeptides of the present disclosure are known in the art and include standard molecular biology techniques for cloning and expressing a polypeptide and chemically synthesizing a polypeptide.

[0541] Peptides can be synthesized by the Fmoc-polyamide mode of solid-phase peptide synthesis as disclosed by Lukas et al. (Lukas et al., 1981) and the references cited therein. The 9-fluorenylmethyloxycarbonyl (Fmoc) group provides temporary N-amino group protection. Repeated cleavage of this highly base-labile protecting group is carried out using 20% ​​piperidine in N,N-dimethylformamide. Side chain functional groups can be protected as their butyl ethers (for serine, threonine, and tyrosine), butyl esters (for glutamic acid and aspartic acid), butyloxycarbonyl derivatives (for lysine and histidine), trityl derivatives (for cysteine), and 4-methoxy-2,3,6-trimethylbenzenesulfonyl derivatives (for arginine). When glutamine or asparagine is the C-terminal residue, the 4,4'-dimethoxybenzhydryl group is used to protect the side chain amide function. The solid-phase support is based on a polydimethyl-acrylamide polymer composed of three monomers: dimethylacrylamide (backbone monomer), bisacryloylethylenediamine (crosslinker), and acryloylsarcosine methyl ester (functionalizing agent). The peptide-to-resin cleavable linker used is an acid-labile 4-hydroxymethyl-phenoxyacetic acid derivative. All amino acid derivatives, except asparagine and glutamine, are added as their preformed symmetrical anhydride derivatives, which are added using a reverse N,N-dicyclohexyl-carbodiimide / 1-hydroxybenzotriazole-mediated coupling procedure. All coupling and deprotection reactions are monitored using ninhydrin, trinitrobenzenesulfonic acid, or isotin test procedures. Upon completion of the synthesis, the peptide is cleaved from the resin support simultaneously with the removal of side-chain protecting groups by treatment with 95% trifluoroacetic acid containing a 50% scavenger mix. Commonly used scavengers include ethanedithiol, phenol, anisole, and water, the exact choice depending on the constituent amino acids of the peptide being synthesized.A combination of solid and solution phase methods for synthesizing peptides is also possible (see, for example, (Bruckdorfer et al., 2004) and references cited therein).

[0542] U.S. Pat. No. 4,897,445 provides a method for solid-phase synthesis of non-peptide bonds (-CH-NH) in polypeptide chains containing polypeptides synthesized by standard procedures, and non-peptide bonds synthesized by reacting amino aldehydes with amino acids in the presence of NaCNBH.

[0543] Vectors and recombinant viruses of the present disclosure The present disclosure also provides vectors comprising the polynucleotides or heterologous polynucleotides of the present disclosure. The present disclosure also provides vectors comprising a polynucleotide encoding one or more of the polypeptides disclosed herein.

[0544] The present disclosure also provides SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 25, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 22 7, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329 , 331, 333, 335, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, or 405, or fragments thereof.

[0545] The present disclosure also relates to SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 4, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 334, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, or 406, or fragments thereof.

[0546] The present disclosure also relates to SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 200, 201, 202, 203 7, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 28 33, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 335, 337, and fragments thereof.

[0547] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 17 6, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 23 0, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 272, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 333 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, and 406, and fragments thereof.

[0548] The present disclosure also relates to SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183 7, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 177, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209 , 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 243, 245, 247, 249, 251, 253, 255, 257, 259, 261, 263, 265, 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 293, 295, 297, 299, 301, 303, 305, 307, 309, 311, 313, 315, 317, 319, 321, 323, 325, 327, 329, 331, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 35, 337, 339, 341, 343, 345, 347, 349, 351, 353, 355, 357, 359, 361, 363, 365, 367, 369, 371, 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 39 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 1 4, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 21

[0013] Also provided are vectors comprising a heterologous polynucleotide encoding a heterologous polypeptide comprising 8, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, or 203 polypeptides.

[0549] The present disclosure also provides SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146 , 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 212, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 244, 246, 248, 250, 252, 254, 256, 258, 260, 262, 264, 266, 268, 270, 2 72, 274, 276, 278, 280, 282, 284, 286, 288, 290, 292, 294, 296, 298, 300, 302, 304, 306, 308, 310, 312, 314, 316, 318, 320, 322, 324, 326, 328, 330, 332, 333 4, 336, 338, 340, 342, 344, 346, 348, 350, 352, 354, 356, 358, 360, 362, 364, 366, 368, 370, 372, 374, 376, 378, 380, 382, ​​384, 386, 388, 390, 392, 394, 396 , 398, 400, 402, 404, and 406, and fragments thereof, selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, or 203 polynucleotides. ,

[0550] In some embodiments, the vector is an expression vector. In some embodiments, the vector is a viral vector.

[0551] In some embodiments, the vector is an expression vector. The vector may be a vector intended for expression of the polynucleotide or heterologous polynucleotide of the present disclosure in any host, such as bacteria, yeast, or mammalian. Suitable expression vectors are typically replicable in the host organism either as episomes or as an integral part of the host chromosomal DNA. Expression vectors usually contain a selection marker, such as ampicillin resistance, hygromycin resistance, tetracycline resistance, kanamycin resistance, or neomycin resistance, to enable detection of cells transformed or transduced with the desired DNA sequence. Exemplary vectors are plasmids, cosmids, phages, viral vectors, transposons, or artificial chromosomes.

[0552] Suitable vectors are known, and many are commercially available for generating recombinant constructs. For example, the following vectors are provided: Bacterial systems: pBs, phagescript, PsiX174, pBluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene, La Jolla, Calif., USA); pTrc99A, pKK223-3, pKK233-3, pDR540, and pRIT5 (Pharmacia, Uppsala, Sweden). Eukaryotic systems: pWLneo, pSV2cat, pOG44, PXR1, pSG (Stratagene), pSVK3, pBPV, pMSG, and pSVL (Pharmacia). Transposon vectors: Sleep Beauty transposon and PiggyBac transposon.

[0553] In some embodiments, the vector is a viral vector. The vectors of the present disclosure can be used to generate recombinant viruses containing the vectors of the present disclosure or to express the polypeptides of the present disclosure. Viral vectors are derived from naturally occurring viral genomes and are typically modified to be replication-deficient, e.g., non-replicating. Non-replicating viruses require proteins to be provided in trans for replication. Typically, these proteins are stably or transiently expressed in virus-producing cell lines, thereby enabling viral replication. Thus, viral vectors are typically infectious and non-replicating. The viral vector may be an adenovirus vector, an adeno-associated virus (AAV) vector (e.g., AAV types 5 and 2), an alphavirus vector (e.g., Venezuelan equine encephalitis virus (VEE), Sindbis virus (SIN), Semliki Forest virus (SFV), and a VEE-SIN chimera), a herpesvirus vector (e.g., a vector derived from a cytomegalovirus, such as rhesus cytomegalovirus (RhCMV)), an arenavirus vector (e.g., a lymphocytic choriomeningitis virus (LCMV) vector), a measles virus vector, a poxvirus vector (e.g., vaccinia virus, modified vaccinia virus Ankara (MVA), NYVAC (derived from the Copenhagen strain of vaccinia), and avipox vectors: canarypox (ALVAC) and fowlpox (FPV) vectors), a vesicular stomatitis virus vector, a retrovirus vector, a lentivirus vector, a virus-like particle, a baculovirus vector, and a bacterial spore.

[0554] The vectors of the present disclosure can be produced using known techniques. The present disclosure also provides recombinant viruses comprising the vectors of the present disclosure.

[0555] Adenovirus vectors In some embodiments, the viral vector is derived from an adenovirus. In some embodiments, the recombinant virus comprising the vector is derived from an adenovirus.

[0556] Adenoviral vectors can be derived from human adenoviruses (Ad), as well as bovine adenoviruses (e.g., bovine adenovirus 3, BAdV3), canine adenoviruses (e.g., CAdV2), porcine adenoviruses (e.g., PAdV3 or 5), or adenoviruses that infect other species, such as great apes, including chimpanzees (Pan), gorillas (Gorilla), orangutans (Pongo), bonobos (Pan paniscus), and common chimpanzees (Pan troglodytes). Typically, naturally occurring great ape adenoviruses are isolated from fecal samples of the respective great apes.

[0557] Human adenoviral vectors can be derived from various adenovirus serotypes, for example, human adenovirus serotypes hAd5, hAd7, hAd11, hAd26, hAd34, hAd35, hAd48, hAd49, or hAd50 (serotypes are also referred to as Ad5, Ad7, Ad11, Ad26, Ad34, Ad35, Ad48, Ad49, or Ad50).

[0558] Great ape adenoviral vectors can be derived from various adenovirus serotypes, for example, great ape adenovirus serotypes GAd20, Gad19, GAd21, GAd25, GAd26, GAd27, GAd28, GAd29, GAd30, GAd31, ChAd3, ChAd4, ChAd5, ChAd6, ChAd7, ChAd8, ChAd9, ChAd10, ChAd11, ChAd16, ChAd17, ChAd19, ChAd20, ChAd22, ChAd24, ChAd26, ChAd30, ChAd31, ChAd37, ChAd38, ChAd44, ChAd55, ChAd63, ChAd73, ChAd82, ChAd83, ChAd146, ChAd147, PanAd1, PanAd2, or PanAd3.

[0559] Adenovirus vectors are known in the art. The sequences of most human and non-human adenoviruses are known, and others can be obtained using standard methods. An exemplary genome sequence of Ad26 can be found in GenBank accession number EF153474 and SEQ ID NO: 1 in WO 2007 / 104792. An exemplary genome sequence of Ad35 can be found in Figure 6 of WO 2000 / 70071. Vectors based on Ad26 are described, for example, in WO 2007 / 104792. Vectors based on Ad35 are described, for example, in U.S. Patent No. 7,270,811 and WO 2000 / 70071. Vectors based on ChAd3, ChAd4, ChAd5, ChAd6, ChAd7, ChAd8, ChAd9, ChAd10, ChAd11, ChAd16, ChAd17, ChAd19, ChAd20, ChAd22, ChAd24, ChAd26, ChAd30, ChAd31, ChAd37, ChAd38, ChAd44, ChAd63, and ChAd82 are described in WO 2005 / 071093. Vectors based on PanAd1, PanAd2, PanAd3, ChAd55, ChAd73, ChAd83, ChAd146, and ChAd147 are described in WO 2010 / 086189.

[0560] Adenoviral vectors are genetically engineered to have at least one gene product essential for viral replication, such as one or more of the adenoviral regions E1, E2, and E4, functionally deleted or completely removed, thereby rendering the adenovirus replication-defective. The deletion of the E1 region may include deletion of E1A, EIB 55K, or EIB 21K, or any combination thereof. Replication-deficient adenoviruses are propagated by providing the proteins encoded in the deleted region in trans with a helper plasmid or by genetically engineering the producer cells to express the required proteins. Adenoviral vectors may also have a deletion in the E3 region, which is not required for replication; therefore, such a deletion does not need to be complemented. The adenoviral vectors of the present disclosure may have at least a portion of the E1 and E3 regions functionally deleted or completely removed. The adenoviral vectors of the present disclosure may further have the E4 and / or E2 regions functionally deleted or completely removed. Suitable producer cells that can be utilized are human retinal cells immortalized with El, such as 911 or PER.C6 cells (see, e.g., U.S. Pat. No. 5,994,128), El-transformed amniotic cells (see, e.g., European Patent No. 1230354), or El-transformed A549 cells (see, e.g., WO 1998 / 39411, U.S. Pat. No. 5,891,690). An exemplary vector that can be used is Ad26, which contains a functional El coding region sufficient for viral replication, a deleted E3 coding region, and a deleted E4 coding region, so long as the E4 open reading frame 6 / 7 is not deleted (see, e.g., U.S. Pat. No. 9,750,801).

[0561] In some embodiments, the adenoviral vector is a human adenovirus (Ad) vector. In some embodiments, the Ad vector is derived from Ad5. In some embodiments, the Ad vector is derived from Ad11. In some embodiments, the Ad vector is derived from Ad26. In some embodiments, the Ad vector is derived from Ad34. In some embodiments, the Ad vector is derived from Ad35. In some embodiments, the Ad vector is derived from Ad48. In some embodiments, the Ad vector is derived from Ad49. In some embodiments, the Ad vector is derived from Ad50.

[0562] In some embodiments, the adenoviral vector is a great ape adenovirus (GAd) vector. In some embodiments, the GAd vector is derived from GAd20. In some embodiments, the GAd vector is derived from GAd19. In some embodiments, the GAd vector is derived from GAd21. In some embodiments, the GAd vector is derived from GAd25. In some embodiments, the GAd vector is derived from GAd26. In some embodiments, the GAd vector is derived from GAd27. In some embodiments, the GAd vector is derived from GAd28. In some embodiments, the GAd vector is derived from GAd29. In some embodiments, the GAd vector is derived from GAd30. In some embodiments, the GAd vector is derived from GAd31. In some embodiments, the GAd vector is derived from ChAd4. In some embodiments, the GAd vector is derived from ChAd5. In some embodiments, the GAd vector is derived from ChAd6. In some embodiments, the GAd vector is derived from ChAd7. In some embodiments, the GAd vector is derived from ChAd8. In some embodiments, the GAd vector is derived from ChAd9. In some embodiments, the GAd vector is derived from ChAd20. In some embodiments, the GAd vector is derived from ChAd22. In some embodiments, the GAd vector is derived from ChAd24. In some embodiments, the GAd vector is derived from ChAd26. In some embodiments, the GAd vector is derived from ChAd30. In some embodiments, the GAd vector is derived from ChAd31. In some embodiments, the GAd vector is derived from ChAd32. In some embodiments, the GAd vector is derived from ChAd33. In some embodiments, the GAd vector is derived from ChAd37. In some embodiments, the GAd vector is derived from ChAd38. In some embodiments, the GAd vector is derived from ChAd44. In some embodiments, the GAd vector is derived from ChAd55. In some embodiments, the GAd vector is derived from ChAd63.In some embodiments, the GAd vector is derived from ChAd68. In some embodiments, the GAd vector is derived from ChAd73. In some embodiments, the GAd vector is derived from ChAd82. In some embodiments, the GAd vector is derived from ChAd83.

[0563] A polypeptide or heterologous polypeptide of the present disclosure can be inserted into a site or region (insertion region) within the vector that does not affect viral viability of the resulting recombinant virus. A polypeptide or heterologous polypeptide of the present disclosure can be inserted in a parallel (transcribed 5' to 3') or antiparallel (transcribed 3' to 5' relative to the vector backbone) orientation to the deleted E1 region. Additionally, suitable transcriptional regulatory elements capable of directing expression of a polypeptide or heterologous polypeptide of the present disclosure in a mammalian host cell in which the vector is prepared for use can be operably linked to a polypeptide or heterologous polypeptide of the present disclosure. "Operably linked" sequences include both expression control sequences adjacent to the nucleic acid sequence they regulate and regulatory sequences at a distance that act in trans to control the nucleic acid sequence being regulated.

[0564] Recombinant adenoviral particles can be prepared and propagated according to any conventional technique in the art (e.g., WO 1996 / 17070) using a complementing cell line or helper virus that provides in trans the defective viral genes necessary for viral replication. Cell lines 293 (Graham et al., 1977, J. Gen. Virol. 36:59-72), PER.C6 (see, e.g., U.S. Pat. No. 5,994,128), E1 A549, and 911 are commonly used to complement E1 deletions. Other cell lines have been genetically engineered to complement defective vectors (Yeh, et al., 1996, J. Virol. 70:559-565; Kroughak and Graham, 1995, Human Gene Ther. 6:1575-1586; Wang, et al., 1995, Gene Ther. 2:775-783; Lusky, et al., 1998, J. Virol. 72:2022-203; EP 919627, and WO 1997 / 04119). Adenoviral particles can be recovered from the culture supernatant as well as from the cells after lysis and, optionally, further purified according to standard techniques (e.g., chromatography, ultracentrifugation as described in WO 1996 / 27677, WO 1998 / 00524, WO 1998 / 26048, and WO 2000 / 50573). Methods for constructing and propagating adenoviral vectors are described, for example, in U.S. Patent Nos. 5,559,099, 5,837,511, 5,846,782, 5,851,806, 5,994,106, 5,994,128, 5,965,541, 5,981,225, 6,040,174, 6,020,191, and 6,113,913.

[0565] The present disclosure provides a recombinant adenovirus comprising a vector of the present disclosure. The present disclosure also provides a recombinant human adenovirus (rAd) comprising a vector of the present disclosure. The present disclosure also provides a recombinant human adenovirus derived from serotype 26 (rAd26) comprising a vector of the present disclosure.

[0566] Provided herein are viral vectors comprising any of the polynucleotides of the present disclosure, wherein the vectors are derived from hAd26 (also referred to as Ad26-bearing).

[0567] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:1, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:1.

[0568] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:3, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:3.

[0569] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:5, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:5.

[0570] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:7, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:7.

[0571] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:9, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:9.

[0572] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:11, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:11.

[0573] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:13, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:13.

[0574] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:15, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:15.

[0575] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:17, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:17.

[0576] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide of SEQ ID NO:19, or having at least 90% sequence identity to SEQ ID NO:19, or at least 95% sequence identity to SEQ ID NO:19, or at least 99% sequence identity to SEQ ID NO:19.

[0577] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide of SEQ ID NO:21, or a polypeptide having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:21.

[0578] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide of SEQ ID NO:23, or a polypeptide having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:23.

[0579] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide encoding an amino acid sequence of SEQ ID NO:25, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:25.

[0580] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide encoding an amino acid sequence of SEQ ID NO:27, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:27.

[0581] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide encoding an amino acid sequence of SEQ ID NO:29, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:29.

[0582] In some embodiments, the Ad26 vector comprises a polynucleotide encoding a polypeptide encoding the amino acid sequence of SEQ ID NO:31, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:31.

[0583] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:33, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:33.

[0584] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:35, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:35.

[0585] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:37, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:37.

[0586] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:39, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:39.

[0587] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:41, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:41.

[0588] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:43, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:43.

[0589] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:45, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:45.

[0590] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:47, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:47.

[0591] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:49, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:49.

[0592] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:51, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:51.

[0593] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:53, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:53.

[0594] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:55, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:55.

[0595] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:57, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:57.

[0596] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:59, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:59.

[0597] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:61, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:61.

[0598] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:63, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:63.

[0599] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:65, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:65.

[0600] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:67, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:67.

[0601] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:69, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:69.

[0602] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:71, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:71.

[0603] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:73, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:73.

[0604] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:75, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:75.

[0605] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:77, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:77.

[0606] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:79, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:79.

[0607] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:81, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:81.

[0608] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:83, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:83.

[0609] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:85, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:85.

[0610] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:87, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:87.

[0611] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:89, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:89.

[0612] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:91, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:91.

[0613] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:93, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:93.

[0614] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:95, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:95.

[0615] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:97, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:97.

[0616] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:99, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:99.

[0617] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:101, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:101.

[0618] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:103, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:103.

[0619] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:105, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:105.

[0620] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:107, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:107.

[0621] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:109, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:109.

[0622] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:111, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:111.

[0623] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:113, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:113.

[0624] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:115, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:115.

[0625] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:117, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:117.

[0626] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:119, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:119.

[0627] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:121, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:121.

[0628] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:123, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:123.

[0629] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:125, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:125.

[0630] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:127, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:127.

[0631] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 129, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 129.

[0632] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:131, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:131.

[0633] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:133, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:133.

[0634] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:135, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:135.

[0635] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:137, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:137.

[0636] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 139, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 139.

[0637] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:141, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:141.

[0638] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:143, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:143.

[0639] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:145, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:145.

[0640] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:147, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:147.

[0641] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:149, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:149.

[0642] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:151, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:151.

[0643] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:153, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:153.

[0644] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:155, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:155.

[0645] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:157, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:157.

[0646] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:159, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:159.

[0647] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:161, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:161.

[0648] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:163, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:163.

[0649] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:165, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:165.

[0650] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:167, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:167.

[0651] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:169, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:169.

[0652] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:171, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:171.

[0653] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:173, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:173.

[0654] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:175, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:175.

[0655] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:177, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:177.

[0656] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 179, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 179.

[0657] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:181, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:181.

[0658] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:183, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:183.

[0659] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:185, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:185.

[0660] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:187, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:187.

[0661] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:189, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:189.

[0662] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:191, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:191.

[0663] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:193, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:193.

[0664] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:195, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:195.

[0665] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:197, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:197.

[0666] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:199, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:199.

[0667] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:201, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:201.

[0668] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:203, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:203.

[0669] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:205, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:205.

[0670] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:207, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:207.

[0671] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:209, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:209.

[0672] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:211, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:211.

[0673] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:213, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:213.

[0674] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:215, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:215.

[0675] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:217, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:217.

[0676] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:219, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:219.

[0677] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:221, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:221.

[0678] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:223, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:223.

[0679] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:225, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:225.

[0680] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:227, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:227.

[0681] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:229, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:229.

[0682] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:231, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:231.

[0683] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:233, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:233.

[0684] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:235, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:235.

[0685] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:237, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:237.

[0686] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:239, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:239.

[0687] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:241, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:241.

[0688] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:243, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:243.

[0689] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:245, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:245.

[0690] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:247, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:247.

[0691] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:249, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:249.

[0692] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:251, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:251.

[0693] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:253, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:253.

[0694] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:255, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:255.

[0695] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:257, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:257.

[0696] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:259, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:259.

[0697] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:261, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:261.

[0698] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:263, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:263.

[0699] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:265, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:265.

[0700] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:267, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:267.

[0701] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:269, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:269.

[0702] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:271, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:271.

[0703] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:273, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:273.

[0704] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:275, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:275.

[0705] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:277, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:277.

[0706] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:279, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:279.

[0707] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:281, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:281.

[0708] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:283, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:283.

[0709] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:285, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:285.

[0710] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:287, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:287.

[0711] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:289, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:289.

[0712] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:291, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:291.

[0713] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:293, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:293.

[0714] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:295, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:295.

[0715] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:297, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:297.

[0716] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:299, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:299.

[0717] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:301, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:301.

[0718] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:303, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:303.

[0719] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:305, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:305.

[0720] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:307, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:307.

[0721] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:309, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:309.

[0722] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:311, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:311.

[0723] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:313, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:313.

[0724] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:315, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:315.

[0725] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:317, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:317.

[0726] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:319, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:319.

[0727] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:321, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:321.

[0728] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:323, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:323.

[0729] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:325, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:325.

[0730] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:327, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:327.

[0731] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:329, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:329.

[0732] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:331, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:331.

[0733] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:333, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:333.

[0734] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:335, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:335.

[0735] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:337, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:337.

[0736] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:339, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:339.

[0737] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:341, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:341.

[0738] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:343, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:343.

[0739] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:345, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:345.

[0740] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:347, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:347.

[0741] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:349, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:349.

[0742] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:351, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:351.

[0743] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:353, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:353.

[0744] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:355, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:355.

[0745] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:357, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:357.

[0746] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:359, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:359.

[0747] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:361, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:361.

[0748] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:363, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:363.

[0749] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:365, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:365.

[0750] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:367, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:367.

[0751] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:369, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:369.

[0752] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:371, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:371.

[0753] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:373, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:373.

[0754] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:375, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:375.

[0755] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:377, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:377.

[0756] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:379, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:379.

[0757] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:381, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:381.

[0758] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:383, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:383.

[0759] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:385, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:385.

[0760] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:387, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:387.

[0761] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:389, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:389.

[0762] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:391, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:391.

[0763] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:393, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:393.

[0764] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:395, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:395.

[0765] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:397, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:397.

[0766] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:399, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:399.

[0767] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:401, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:401.

[0768] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:403, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:403.

[0769] In some embodiments, the Ad26 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:405, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:405.

[0770] In some embodiments, the Ad26 vector comprises SEQ ID NOs: 1, 3, 5, 11, 15, 17, 19, 21, 25, 29, 31, 33, 39, 43, 45, 49, 53, 59, 63, 65, 67, 81, 85, 87, 89, 91, 95, 97, 111, 113, 115, 119, 123, 127, 129, 145, 177, 179, 181, 183, 185, 187, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 215, 219, 221, 223, 229, 233, 235, 237, 239, 241, 243, 245, 247, 251, 255, 257, 259, 261, 263, 267, 271, 279, 281, 285, 293, 295, 297, 301, 303, 305, 307, 309, 319, 323, 325, 337, 339, 343, 345, 349, 371, and 375, and fragments thereof.

[0771] The present disclosure also provides a recombinant great ape adenovirus (rGAd) comprising a vector of the present disclosure. In some embodiments, the rGAd is derived from GAd20. In some embodiments, the rGAd is derived from GAd19. In some embodiments, the rGAd is derived from GAd21. In some embodiments, the rGAd is derived from GAd25. In some embodiments, the rGAd is derived from GAd26. In some embodiments, the rGAd is derived from GAd27. In some embodiments, the rGAd is derived from GAd28. In some embodiments, the rGAd is derived from GAd29. In some embodiments, the rGAd is derived from GAd30. In some embodiments, the rGAd is derived from GAd31. GAd19-21 and GAd25-31 are described in WO 2019 / 008111 and represent strains that are highly immunogenic in the general human population and lack pre-existing immunity. The polynucleotide sequence of the GAd20 genome is disclosed in WO 2019 / 008111.

[0772] Also provided herein is a recombinant chimpanzee adenovirus (rChAd20) derived from serotype 20 comprising a vector of the present disclosure. In some embodiments, the viral vector comprising any of the polynucleotides of the present disclosure is a vector derived from GAd20.

[0773] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:1, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:1.

[0774] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:3, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:3.

[0775] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:5, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:5.

[0776] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:7, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:7.

[0777] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:9, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:9.

[0778] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:11, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:11.

[0779] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:13, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:13.

[0780] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:15, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:15.

[0781] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 17, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 17.

[0782] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:19, or having at least 90% sequence identity to SEQ ID NO:19, or at least 95% sequence identity to SEQ ID NO:19, or at least 99% sequence identity to SEQ ID NO:19.

[0783] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:21, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:21.

[0784] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:23, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:23.

[0785] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:25, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:25.

[0786] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:27, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:27.

[0787] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:29, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:29.

[0788] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:31, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:31.

[0789] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:33, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:33.

[0790] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:35, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:35.

[0791] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:37, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:37.

[0792] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:39, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:39.

[0793] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:41, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:41.

[0794] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:43, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:43.

[0795] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:45, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:45.

[0796] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:47, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:47.

[0797] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:49, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:49.

[0798] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:51, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:51.

[0799] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:53, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:53.

[0800] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:55, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:55.

[0801] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:57, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:57.

[0802] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:59, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:59.

[0803] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:61, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:61.

[0804] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:63, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:63.

[0805] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:65, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:65.

[0806] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:67, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:67.

[0807] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:69, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:69.

[0808] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:71, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:71.

[0809] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:73, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:73.

[0810] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 75, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 75.

[0811] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:77, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:77.

[0812] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:79, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:79.

[0813] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:81, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:81.

[0814] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:83, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:83.

[0815] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:85, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:85.

[0816] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:87, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:87.

[0817] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:89, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:89.

[0818] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:91, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:91.

[0819] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:93, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:93.

[0820] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:95, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:95.

[0821] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:97, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:97.

[0822] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:99, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:99.

[0823] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:101, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:101.

[0824] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:103, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:103.

[0825] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:105, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:105.

[0826] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:107, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:107.

[0827] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:109, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:109.

[0828] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:111, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:111.

[0829] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:113, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:113.

[0830] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:115, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:115.

[0831] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:117, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:117.

[0832] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:119, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:119.

[0833] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:121, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:121.

[0834] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 123, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 123.

[0835] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 125, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 125.

[0836] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 127, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 127.

[0837] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 129, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 129.

[0838] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:131, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:131.

[0839] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 133, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 133.

[0840] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 135, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 135.

[0841] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 137, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 137.

[0842] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 139, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 139.

[0843] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 141, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 141.

[0844] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 143, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 143.

[0845] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 145, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 145.

[0846] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 147, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 147.

[0847] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 149, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 149.

[0848] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:151, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:151.

[0849] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 153, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 153.

[0850] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 155, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 155.

[0851] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 157, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 157.

[0852] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 159, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 159.

[0853] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:161, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:161.

[0854] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 163, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 163.

[0855] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 165, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 165.

[0856] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 167, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 167.

[0857] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 169, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 169.

[0858] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 171, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 171.

[0859] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 173, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 173.

[0860] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 175, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 175.

[0861] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 177, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 177.

[0862] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 179, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 179.

[0863] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:181, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:181.

[0864] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 183, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 183.

[0865] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 185, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 185.

[0866] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 187, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 187.

[0867] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 189, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 189.

[0868] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:191, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:191.

[0869] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 193, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 193.

[0870] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 195, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 195.

[0871] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:197, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:197.

[0872] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 199, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 199.

[0873] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:201, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:201.

[0874] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:203, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:203.

[0875] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:205, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:205.

[0876] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:207, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:207.

[0877] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:209, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:209.

[0878] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:211, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:211.

[0879] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:213, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:213.

[0880] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:215, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:215.

[0881] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:217, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:217.

[0882] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:219, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:219.

[0883] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:221, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:221.

[0884] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:223, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:223.

[0885] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO: 225, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO: 225.

[0886] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:227, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:227.

[0887] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:229, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:229.

[0888] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:231, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:231.

[0889] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:233, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:233.

[0890] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:235, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:235.

[0891] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:237, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:237.

[0892] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:239, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:239.

[0893] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:241, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:241.

[0894] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:243, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:243.

[0895] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:245, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:245.

[0896] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:247, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:247.

[0897] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:249, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:249.

[0898] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:251, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:251.

[0899] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:253, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:253.

[0900] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:255, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:255.

[0901] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:257, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:257.

[0902] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:259, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:259.

[0903] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:261, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:261.

[0904] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:263, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:263.

[0905] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:265, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:265.

[0906] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:267, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:267.

[0907] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:269, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:269.

[0908] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:271, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:271.

[0909] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:273, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:273.

[0910] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:275, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:275.

[0911] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:277, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:277.

[0912] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:279, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:279.

[0913] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:281, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:281.

[0914] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:283, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:283.

[0915] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:285, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:285.

[0916] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:287, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:287.

[0917] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:289, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:289.

[0918] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:291, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:291.

[0919] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:293, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:293.

[0920] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:295, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:295.

[0921] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:297, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:297.

[0922] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:299, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:299.

[0923] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:301, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:301.

[0924] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:303, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:303.

[0925] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:305, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:305.

[0926] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:307, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:307.

[0927] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:309, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:309.

[0928] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO:311, or having at least 90% sequence identity, or at least 95% sequence identity, or at least 99% sequence identity to SEQ ID NO:311.

[0929] In some embodiments, the GAd20 vector comprises a polynucleotide encoding the amino acid sequence of SEQ I...

Claims

1. A polypeptide comprising: A polypeptide comprising the amino acid sequence of SEQ ID NOs: 1, 3, 5, 25, 31, 49, 53, 65, 85, 87, 111, 115, 127, 129, 177, 179, 183, 187, 191, 193, 195, 201, 207, 219, 221, 223, 229, 251, 261, 323, 337, 339, 349, 375, 379, 381, 389, 391, 393, 395, 397, 401, 403, and 405.

2. The polypeptide of claim 1 , wherein the amino acid sequences are linked to each other in any order.

3. The polypeptide of claim 1, wherein the amino acid sequences are linked to each other in any order without a linker.

4. 4. The polypeptide of claim 1, wherein the polypeptide comprises one or more reverse peptide bonds, D-isomers of amino acids, chemical modifications, or any combination thereof.

5. A polynucleotide encoding the polypeptide of any one of claims 1 to 4.

6. 6. The polynucleotide of claim 5, wherein the polynucleotide comprises SEQ ID NOs: 2, 4, 6, 26, 32, 50, 54, 66, 86, 88, 112, 116, 128, 130, 178, 180, 184, 188, 192, 194, 196, 202, 208, 220, 222, 224, 230, 252, 262, 324, 338, 340, 350, 376, 380, 382, ​​390, 392, 394, 396, 398, 402, 404, and 406.

7. The polynucleotide of claim 5 or 6, wherein the polynucleotide comprises DNA or RNA.

8. The polynucleotide of claim 7 , wherein the RNA is mRNA.

9. A vector comprising the polynucleotide according to any one of claims 5 to 8.

10. 10. The vector of claim 9, wherein the vector is selected from an adenoviral vector, a poxvirus vector, an adeno-associated virus vector, a retroviral vector, a self-replicating RNA molecule, and combinations thereof.

11. The adenoviral vector is selected from the group consisting of hAd5, hAd7, hAd11, hAd26, hAd34, hAd35, hAd48, hAd49, hAd50, GAd20, GAd19, GAd21, GAd25, GAd26, GAd27, GAd28, GAd29, GAd30, GAd31, ChAd3, ChAd4, ChAd5, ChAd6, ChAd7, ChAd8, ChAd9, ChAd10, ChAd 11, ChAd16, ChAd17, ChAd19, ChAd20, ChAd22, ChAd24, ChAd26, ChAd30, ChAd31, ChAd37, ChAd38, ChAd44, ChAd55, ChAd63, ChAd73, ChAd82, ChAd83, ChAd146, ChAd147, PanAdl, PanAd2, or PanAd3.

12. 11. The vector of claim 10, wherein the poxvirus vector is selected from a smallpox virus vector, a vaccinia virus vector, a cowpox virus vector, a monkeypox virus vector, a Copenhagen vaccinia virus (W) vector, a New York attenuated vaccinia virus (NYVAC) vector, and a modified vaccinia Ankara (MVA) vector.

13. The vector of claim 10 , wherein the vector is an adenoviral vector.

14. The vector of claim 10 , wherein the vector is a poxvirus vector.

15. The vector of claim 10 , wherein the vector is a self-replicating RNA molecule.

16. The vector of claim 11 , wherein the adenoviral vector is an hAd26 vector.

17. The vector of claim 11 , wherein the adenoviral vector is a GAd20 vector.

18. The vector of claim 10 , wherein the poxvirus vector is an MVA vector.

19. The vector of claim 10 , wherein the vector is a self-replicating RNA molecule.

20. A pharmaceutical composition comprising the polypeptide according to any one of claims 1 to 4.

21. A pharmaceutical composition comprising the polynucleotide according to any one of claims 5 to 8.

22. A pharmaceutical composition comprising the vector according to any one of claims 9 to 19.

23. 23. The pharmaceutical composition of claim 22, wherein the vector is a recombinant virus selected from Ad26 virus, MVA virus, GAd20 virus, and combinations thereof.

24. The pharmaceutical composition according to any one of claims 20 to 23, the pharmaceutical composition is for use in a method of inducing an immune response in a subject; The method comprises administering the pharmaceutical composition to the subject in need thereof to induce the immune response.

25. 1. A pharmaceutical composition for use in a method of inducing an immune response in a subject, comprising: the pharmaceutical composition comprises a recombinant virus or self-replicating RNA molecule comprising a polynucleotide encoding the amino acid sequence of SEQ ID NOs: 1, 3, 5, 25, 31, 49, 53, 65, 85, 87, 111, 115, 127, 129, 177, 179, 183, 187, 191, 193, 195, 201, 207, 219, 221, 223, 229, 251, 261, 323, 337, 339, 349, 375, 379, 381, 389, 391, 393, 395, 397, 401, 403, and 405; The method comprises administering the pharmaceutical composition to the subject in need thereof; the recombinant virus is selected from Ad26, MVA, or GAd20; said administering comprising one or more administrations of said pharmaceutical composition; Pharmaceutical compositions.

26. The pharmaceutical composition according to any one of claims 20 to 23, the pharmaceutical composition is for use in a method for treating, preventing, reducing the risk of developing, or delaying the onset of ovarian cancer in a subject; The method comprises administering the pharmaceutical composition to the subject in need thereof to treat, prevent, reduce the risk of developing, or delay the onset of ovarian cancer.

27. 1. A pharmaceutical composition for use in a method for treating, preventing, reducing the risk of developing, or delaying the onset of ovarian cancer in a subject, comprising: the pharmaceutical composition comprises a recombinant virus or self-replicating RNA molecule comprising a polynucleotide encoding the amino acid sequence of SEQ ID NOs: 1, 3, 5, 25, 31, 49, 53, 65, 85, 87, 111, 115, 127, 129, 177, 179, 183, 187, 191, 193, 195, 201, 207, 219, 221, 223, 229, 251, 261, 323, 337, 339, 349, 375, 379, 381, 389, 391, 393, 395, 397, 401, 403, and 405; The method comprises administering to the subject in need thereof the pharmaceutical composition to treat, prevent, reduce the risk of developing, or delay the onset of ovarian cancer; the recombinant virus is selected from Ad26, MVA, or GAd20; said administering comprising one or more administrations of said pharmaceutical composition; Pharmaceutical compositions.

28. 28. The pharmaceutical composition of any one of claims 24 to 27, wherein the subject expresses one or more polypeptides of SEQ ID NOs: 1, 3, 5, 25, 31, 49, 53, 65, 85, 87, 111, 115, 127, 129, 177, 179, 183, 187, 191, 193, 195, 201, 207, 219, 221, 223, 229, 251, 261, 323, 337, 339, 349, 375, 379, 381, 389, 391, 393, 395, 397, 401, 403, and 405.

29. 29. The pharmaceutical composition of claim 28, wherein the one or more polypeptides are present at a frequency of at least about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, or about 70% or more in the population of subjects with ovarian cancer.

30. 28. The pharmaceutical composition of claim 26 or 27, wherein the ovarian cancer is recurrent ovarian cancer, refractory ovarian cancer, metastatic ovarian cancer, platinum-resistant ovarian cancer, or any combination thereof.

31. 30. The pharmaceutical composition of claim 28 or 29, wherein the subject is treatment-naive.

32. 30. The pharmaceutical composition of claim 28 or 29, wherein the subject has undergone surgery.

33. 30. The pharmaceutical composition of claim 28 or 29, wherein the subject has elevated levels of cancer antigen 125 (CA125).

34. The pharmaceutical composition of any one of claims 27 to 33, wherein the method further comprises administering to the subject an additional cancer therapeutic agent.

35. 35. The pharmaceutical composition of claim 34, wherein the additional cancer therapeutic agent is surgery, chemotherapy, radiation, a checkpoint inhibitor, targeted therapy, or any combination thereof.

36. the additional cancer therapeutic agent is a CTLA-4 antibody, a CTLA-4 ligand, a PD-1 axis inhibitor, a PD-L1 axis inhibitor, a TLR agonist, a CD40 agonist, an OX40 agonist, hydroxyurea, ruxolitinib, fedratinib, a 4-1BB agonist, a CD28 agonist, a STING antagonist, a RIG-1 antagonist, a TCR-T therapy, a CAR-T therapy, a FLT3 ligand, or sulfate.

36. The pharmaceutical composition of claim 35, which is aluminum, a BTK inhibitor, a CD38 antibody, a CDK inhibitor, a CD33 antibody, a CD37 antibody, a CD25 antibody, a GM-CSF inhibitor, IL-2, IL-15, IL-7, a CD3 redirection molecule, pomalimib, IFNγ, IFNα, TNFα, a VEGF antibody, a CD70 antibody, a CD27 antibody, a BCMA antibody, a GPRC5D antibody, or any combination thereof.

37. 36. The pharmaceutical composition of claim 35, wherein the checkpoint inhibitor is ipilimumab, cetrelimab, pembrolizumab, nivolumab, sintilimab, cemiplimab, toripalimab, camrelizumab, tislelizumab, dostralimab, spartalizumab, prorugolimab, balstilimab, budigalimab, sasanlimab, avelumab, atezolizumab, durvalumab, embafolimab, iodapolimab, or any combination thereof.

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