Simian Subfamily B Adenoviruses SAdV-28, -27, -29, -32, -33, and -35 and Uses Thereof

Abstract

A recombinant vector comprises simian adenovirus 28, simian adenovirus 27, simian adenovirus 32, simian adenovirus 33, and/or simian adenovirus 35 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-28, -27, -32, -33, or -35 genes is also disclosed. Methods of using the vectors and cell lines are provided.

1 . An adenovirus having a capsid comprising a capsid protein selected from the group consisting of:
 (a) a hexon protein of SAdV-29, amino acids 1 to 954 of SEQ ID NO: 81; a hexon protein of SAdV-32, amino acids 1 to 955 of SEQ ID NO: 113; a hexon protein of SAdV-33, amino acids 1 to 951 of SEQ ID NO: 144; a hexon protein of SAdV-35, amino acids 1 to 956 of SEQ ID NO: 176;   (b) a penton protein of SAdV-28, amino acids 1 to 582 of SEQ ID NO: 6; a penton protein of SAdV-27, amino acids 1 to 562 of SEQ ID NO: 44; a penton protein of SAdV-29, amino acids 1 to 576 of SEQ ID NO: 76; a penton protein of SAdV-32, amino acids 1 to 585 of SEQ ID NO: 108; a penton protein of SAdV-33, amino acids 1 to 571 of SEQ ID NO: 139; a penton protein of SAdV-35, amino acids 1 to 563 of SEQ ID NO: 171; and   (c) a fiber protein of SAdV-28, amino acids 1 to 323 of SEQ ID NO: 21, a fiber protein of SAdV-27, amino acids 1 to 325 of SEQ ID NO: 59; a fiber protein of SAdV-29, amino acids 1 to 324 of SEQ ID NO: 91; a fiber protein of SAdV-32, amino acids 1 to 319 of SEQ ID NO: 123; a fiber protein of SAdV-33, amino acids 1 to 325 of SEQ ID NO: 154; a fiber protein of SAdV-35, amino acids 1 to 353 of SEQ ID NO: 185;   said capsid encapsidating a heterologous nucleic acid comprising a gene operably linked to expression control sequences which direct transcription, translation, and/or expression thereof in a host cell.   
     
     
         2 . The adenovirus according to  claim 1 , further comprising a 5′ and a 3′ adenovirus cis-element necessary for replication and encapsidation. 
     
     
         3 . The adenovirus according to  claim 1 , wherein said adenovirus lacks all or a part of the E1 gene. 
     
     
         4 . The adenovirus according to  claim 3 , wherein said adenovirus is replication-defective. 
     
     
         5 . The adenovirus according to  claim 3 , wherein said adenovirus has a hybrid capsid. 
     
     
         6 . The adenovirus according to  claim 5 , wherein said hybrid capsid comprises at least one capsid protein from one or more adenoviruses selected from SAdV-28, SAdV-27, SAdV-32, SAdV-33, and SAdV-35. 
     
     
         7 . The adenovirus according to  claim 1 , wherein said adenovirus is a pseudotyped adenovirus. 
     
     
         8 . The adenovirus according to  claim 1 , wherein the recombinant adenovirus comprises one or more adenovirus genes. 
     
     
         9 . A composition comprising an adenovirus according to  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         10 . A method for targeting a cell having an adenoviral receptor comprising delivering to a subject an adenovirus according to  claim 1 . 
     
     
         11 . A composition comprising the adenovirus according to  claim 1 , further comprising one or more simian adenovirus proteins selected from the group consisting of:
 E1a, SEQ ID NO: 30, 68, 95, 131, 163 or 195;   E1b, small T/19K, SEQ ID NO: 23, 61, 93, 125, 156, or 187;   E1b, large T/55K, SEQ ID NO: 2, 40, 73, 104, 135, or 167;   IX, SEQ ID NO: 3, 41, 73, 105, 136, or 168;   52/55D, SEQ ID NO: 4, 42, 74, 106, 137, or 169;   IIIa, SEQ ID NO: 5, 43, 75, 107, 138, or 170;   Penton, SEQ ID NO: 6, 44, 76, 108, 139, or 171;   VII, SEQ ID NO: 7, 45, 77, 109, 140, and 172;   V, SEQ ID NO: 8, 46, 78, 110, 141 or 173;   pX, SEQ ID NO: 9, 47, 79, 111, 142 or 174;   VI, SEQ ID NO: 10, 48, 80, 112, 143, or 175;   Hexon, SEQ ID NO: 11, 49, 81, 113, 144, or 176;   Endoprotease, SEQ ID NO: 12, 50, 82, 114, 145, or 189;   100 kD, SEQ ID NO: 13, 51, 83, 115, 146, or 177;   33 kD, SEQ ID NO: 32, 70, 97, 133, 165, or 197;   22 kD, SEQ ID NO: 25, 63, 99, 127, 158, or 190;   VIII, SEQ ID NO: 14, 52, 84, 116, 147, or 178;   E3/12.5 K, SEQ ID NO: 15, 53, 100, 117, 148, or 179;   CR1-alpha, SEQ ID NO: 26, 64, 85, 128, 159, or 191;   gp19K, SEQ ID NO: 16, 54, 101, 118, 149, or 180;   CR1-beta, SEQ ID NO: 27, 55, 86, 119, 160 or 192;   CR1-gamma, SEQ ID NO: 17, 56, 87, 120, 150 or 181;   CR1-delta, SEQ ID NO: 18, 57, 88, 151 or 182;   RID-alpha, SEQ ID NO: 19, 65, 89, 121, 152 or 183;   RID-beta, SEQ ID NO: 28, 58, 102, 129, 161, or 193;   E3/14.7K, SEQ ID NO: 20, 66, 90, 122, 153 or 184; and   Fiber, SEQ ID NO: 21, 59, 91, 123, 154 or 185.   
     
     
         12 . A method for targeting a cell having an adenoviral receptor comprising delivering to a subject a composition according to  claim 11 .