Simian adenoviral vectors with two expression cassettes

Abstract

A simian adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, and wherein the first expression cassette is inserted in the E1 region of the simian adenoviral vector, and the second expression cassette is inserted in a region of the adenoviral vector that is compatible with vector replication.

1 - 22 . (canceled) 
     
     
         23 . A simian adenoviral vector comprising two expression cassettes, wherein each expression cassette comprises a transgene and a promoter, wherein the first expression cassette is inserted in the E1 region of the simian adenoviral vector, and the second expression cassette is inserted in a region of the adenoviral vector that is compatible with vector replication. 
     
     
         24 . The simian adenoviral vector of  claim 23 , wherein the second expression cassette is inserted in the E3 region, between the stop codons of L5 and E4 (the “HE1” region) or between the end of the ITR and the cap site of E4 mRNA (the “HE2” region) of the simian adenoviral vector. 
     
     
         25 . The simian adenoviral vector of  claim 24 , wherein the second expression cassette is inserted in the E3 region of the simian adenoviral vector. 
     
     
         26 . The simian adenoviral vector of  claim 24 , wherein the second expression cassette is inserted in the HE1 region of the simian adenoviral vector. 
     
     
         27 . The simian adenoviral vector of  claim 24 , wherein the second expression cassette is inserted in the HE2 region of the simian adenoviral vector. 
     
     
         28 . The simian adenoviral vector of  claim 23 , wherein the vector is a chimpanzee adenoviral vector. 
     
     
         29 . The simian adenoviral vector of  claim 23 , wherein the vector is an adenovirus. 
     
     
         30 . The simian adenoviral vector of  claim 29 , wherein the adenovirus is ChAd155. 
     
     
         31 . The simian adenoviral vector of  claim 29 , wherein the adenovirus is ChAd83. 
     
     
         32 . The simian adenoviral vector of  claim 23 , wherein the first expression cassette and/or the second expression cassette comprises a human CMV or an enhanced human CMV promoter. 
     
     
         33 . The simian adenoviral vector of  claim 32 , wherein the enhanced hCMV promoter has a nucleic acid sequence having at least about 90% sequence identity to SEQ ID NO: 6. 
     
     
         34 . The simian adenoviral vector of  claim 33 , wherein the enhanced hCMV promoter has a nucleic acid sequence having at least about 96% sequence identity to SEQ ID NO: 6. 
     
     
         35 . The simian adenoviral vector of  claim 32 , wherein the promoter comprises the nucleic acid sequence of SEQ ID NO: 6. 
     
     
         36 . The simian adenoviral vector of  claim 23 , wherein the first and second expression cassettes comprise different promoters. 
     
     
         37 . The simian adenoviral vector of  claim 23 , wherein the adenoviral vector is capable of infecting a mammalian cell. 
     
     
         38 . The simian adenoviral vector of  claim 23 , wherein the first and/or the second expression cassette further comprises a posttranscriptional regulatory element. 
     
     
         39 . The simian adenoviral vector of  claim 38 , wherein the posttranscriptional regulatory element is a Woodchuck Hepatitis Postranscriptional Regulatory Element. 
     
     
         40 . A composition comprising the simian adenoviral vector of  claim 23  and a pharmaceutically acceptable excipient. 
     
     
         41 . A method of inducing an immune response against a disease caused by a pathogen in a subject in need thereof comprising administering an immunologically effective amount of the simian adenoviral vector of  claim 23  to the subject. 
     
     
         42 . The method of  claim 41 , wherein the simian adenoviral vector is a vaccine component.