Simian Adenoviruses SAdV-36, -42.1, -42.2, and -44 and Uses Thereof

Abstract

A recombinant vector comprises simian adenovirus 36, simian adenovirus 42.1, simian adenovirus 42.2 and/or simian adenovirus 44 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-36, -42.1, -42.2 or -44 gene(s) is also described. Methods of using the vectors and cell lines are provided.

1 . A recombinant adenovirus having a capsid comprising a hexon protein, a penton protein, and a fiber protein, wherein said hexon protein is the hexon protein of SAdV-44, amino acids 1 to 962 of SEQ ID NO: 105;
 said capsid encapsidating a heterologous nucleic acid molecule carrying a gene sequence operably linked to expression control sequences which direct transcription, translation, or expression in a host cell.   
     
     
         2 . The adenovirus according to  claim 1 , further comprising 5′ and 3′ adenovirus cis-elements 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 1 , wherein said virus has a hybrid capsid. 
     
     
         6 . The adenovirus according to  claim 5 , wherein said capsid comprises a SAdV-42.1, SAdV-42.2 or SAdV-44 fiber protein. 
     
     
         7 . The adenovirus according to  claim 5 , wherein the capsid comprises a SAdV-42.1, SAdV-42.2 or SAdV-44 penton protein. 
     
     
         8 . A recombinant adenovirus having a capsid comprising a hexon containing a fragment of the simian adenovirus (SAdV) hexon protein and a nucleic acid sequence heterologous to the SAdV, wherein the fragment of the SAdV hexon protein is the SAdV hexon protein of SEQ ID NO:43, 74 or 105 with an N-terminal or C-terminal truncation of about 50 amino acids in length or is selected from the group consisting of:
 amino acid residues 125 to 443 of SEQ ID NO:43, 74 or 105;   amino acid residues 138 to 441 of SEQ ID NO:43, 74 or 105;   amino acid residues 138 to 163 of SEQ ID NO:43, 74 or 105;   amino acid residues 170 to 176 of SEQ ID NO:43, 74 or 105; and   amino acid residues 404 to 430 of SEQ ID NO:43, 74 or 105.   
     
     
         9 . The recombinant adenovirus according to  claim 8 , wherein the capsid further comprises a SAdV-42.1, SAdV-42.2 or SAdV-44 fiber protein. 
     
     
         10 . The recombinant adenovirus according to  claim 8 , wherein the capsid further comprises a SAdV-42.1, SAdV-42.2 or SAdV-44 penton protein. 
     
     
         11 . The recombinant adenovirus according to  claim 8 , wherein said adenovirus is a pseudotyped adenovirus comprising 5′ and 3′ adenovirus cis-elements necessary for replication and encapsidation, said cis-elements comprising an adenovirus 5′ inverted terminal repeat and an adenovirus 3′ inverted terminal repeat. 
     
     
         12 . The recombinant adenovirus according to  claim 8 , wherein the adenovirus comprises a nucleic acid sequence encoding a product operatively linked to sequences which direct expression of said product in a host cell. 
     
     
         13 . The recombinant adenovirus according to  claim 8 , wherein the recombinant adenovirus comprises one or more adenovirus genes. 
     
     
         14 . The recombinant adenovirus according to  claim 8 , wherein the recombinant adenovirus is replication-defective. 
     
     
         15 . The recombinant adenovirus according to  claim 14 , wherein the recombinant adenovirus is deleted in adenovirus E1. 
     
     
         16 . A composition comprising an adenovirus according to  claim 1  in a pharmaceutically acceptable carrier. 
     
     
         17 . A method for targeting a cell having an adenoviral receptor comprising delivering to a subject a virus according to  claim 1 . 
     
     
         18 . A vector comprising a simian adenovirus (SAdV) nucleic acid sequence selected from one or more of the group consisting of:
 (a) 5′ inverted terminal repeat (ITR) sequences;   (b) the adenovirus E1a region;   (c) the adenovirus E1b region, or a fragment thereof selected from among the group consisting of the open reading frames for the small T, large T, and IX regions;   (d) the E2b region, or a fragment thereof selected from the group consisting of the open reading frames for pTP, polymerase, and IVa2;   (e) the L1 region, or a fragment thereof selected from among the group consisting of the open reading frames for the 52/55 kD protein and IIIa protein;   (f) the L2 region, or a fragment thereof selected from the group consisting of the open reading frames for the penton, VII, V, and pX/Mu proteins;   (g) the L3 region, or a fragment thereof selected from the group consisting of the open reading frames for the VI, hexon, or endoprotease;   (h) the E2a region or the open reading frame for the DNA binding protein (DBP);   (i) the L4 region, or a fragment thereof selected from the group consisting of the open reading frames for the 100 kD protein, the 33 kD homolog, the 22 kD protein, and VIII;   (j) the E3 region, or a fragment thereof selected from the group consisting of the open reading frames for the 12.5K protein, CR1-alpha, gp19K, CR1-beta, CR1-gamma, RID-alpha, RID-beta, and 14.7K protein;   (k) the L5 region, or the open reading frame for the fiber protein;   (l) the E4 region, or a fragment thereof selected from the group consisting of the open reading frames for the E4 ORF6/7, E4 ORF6, E4 ORF4, E4 ORF3, E4 ORF2, and E4 ORF1; and   (m) the 3′ ITR;   of SAdV-42.1, SEQ ID NO:33, SAdV-42.2, SEQ ID NO:64, or SAdV-44, SEQ ID NO:95.   
     
     
         19 . A simian adenovirus protein encoded by the vector according to  claim 18 . 
     
     
         20 . A composition comprising an adenovirus according to  claim 1 , wherein said adenovirus comprises one or more simian adenovirus proteins selected from the group consisting of:
 E1a, SEQ ID NO:61, 92 or 123;   E1b, small T/19K, SEQ ID NO: 54, 65 or 96;   E1b, large T/55K, SEQ ID NO: 34, 85 or 116;   IX, SEQ ID NO:3 5, 66 or 97;   52/55D, SEQ ID NO: 36, 67 or 98;   IIIa, SEQ ID NO: 37, 68 or 99;   Penton, SEQ ID NO: 38, 69 or 100;   VII, SEQ ID NO: 39, 70 or 101;   V, SEQ ID NO: 40, 71 or 102;   pX, SEQ ID NO: 41, 72 or 103;   VI, SEQ ID NO: 42, 73 or 104;   Hexon, SEQ ID NO: 43, 74 or 105;   Endoprotease, SEQ ID NO: 44, 75 or 106;   100 kD, SEQ ID NO: 45, 76 or 107;   33 kD, SEQ ID NO: 63, 94 or 125;   22 kD, SEQ ID NO: 56, 87 or 118;   VIII, SEQ ID NO: 46, 77 or 108;   12.5 K, SEQ ID NO: 57, 78 or 109;   CR1-alpha, SEQ ID NO: 47, 88 or 110;   gp19K, SEQ ID NO: 48, 79 or 111;   CR1-beta, SEQ ID NO:49, 80 or 112;   CR1-gamma, SEQ ID NO: 58, 89 or 119;   RID-alpha, SEQ ID NO: 50, 81 or 113;   RID-beta, SEQ ID NO: 51, 82 or 114;   E3/14.7K, SEQ ID NO: 59, 90 or 120; and   Fiber, SEQ ID NO: 52, 83 or 121.