Simian adenoviruses SAdV-36, -42.1, -42.2, and -44 and uses thereof
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:
(a) the hexon protein of Simian Adenovirus 42.1 (SAdV-42.1), amino acids 1 to 957 of SEQ ID NO: 43;
(b) the hexon protein of SAdV-42.2, amino acids 1 to 957 of SEQ ID NO: 74; or
(c) the hexon protein of SAdV-44, amino acids 1 to 962 of SEQ ID NO: 105;
said capsid encapsidating a heterologous nucleic acid molecule comprising a gene sequence operably linked to expression control sequences which direct transcription, translation, or expression in a host cell.
2. The recombinant adenovirus according to claim 1 , further comprising a 5′ and a 3′ adenovirus cis-element necessary for replication and encapsidation.
3. The recombinant adenovirus according to claim 1 , wherein said recombinant adenovirus lacks all or a part of the E1 gene.
4. The recombinant adenovirus according to claim 3 , wherein said recombinant adenovirus is replication-defective.
5. The recombinant adenovirus according to claim 1 , wherein said capsid is a hybrid capsid.
6. The recombinant adenovirus according to claim 5 , wherein the hybrid capsid comprises the fiber protein of SAdV-42.1, SAdV-42.2 or SAdV-44.
7. The recombinant adenovirus according to claim 5 , wherein the hybrid capsid comprises the penton protein of SAdV-42.1, SAdV-42.2 or SAdV-44.
8. The recombinant adenovirus according to claim 1 , wherein said recombinant adenovirus is a pseudotyped adenovirus comprising a 5′ and a 3′ adenovirus cis-element necessary for replication and encapsidation, said cis-elements comprising an adenovirus 5′ inverted terminal repeat and an adenovirus 3′ inverted terminal repeat.
9. The recombinant adenovirus according to claim 1 , wherein the recombinant adenovirus comprises one or more adenovirus genes.
10. The recombinant adenovirus according to claim 1 , wherein the recombinant adenovirus is replication-defective.
11. The recombinant adenovirus according to claim 10 , wherein the recombinant adenovirus comprises a deletion in the adenovirus E1 region.
12. A composition comprising the recombinant adenovirus according to claim 1 in a pharmaceutically acceptable carrier.
13. A composition comprising the recombinant adenovirus according to claim 1 , wherein said recombinant adenovirus further 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;
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 IDNO: 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.