Modified serotype 28 adenoviral vectors

Abstract

The invention provides a replication-deficient serotype 28 adenoviral vector characterized by comprising a portion of a serotype 45 adenoviral hexon protein and/or a portion of a serotype 45 fiber protein in place of the endogenous serotype 28 hexon and/or fiber protein.

1 . A replication-deficient serotype 28 adenoviral vector comprising one or both of the following:
 (a) at least a portion of an adenovirus serotype 45 hexon protein in place of at least a portion of the endogenous serotype 28 hexon protein, and   (b) at least a portion of an adenovirus serotype 45 fiber protein in place of at least a portion of the endogenous serotype 28 fiber protein.   
     
     
         2 . The adenoviral vector of  claim 1 , which comprises at least a portion of an adenovirus serotype 45 hexon protein in place of at least a portion of the endogenous serotype 28 hexon protein, or at least a portion of an adenovirus serotype 45 fiber protein in place of at least a portion of the endogenous serotype 28 fiber protein. 
     
     
         3 . The adenoviral vector of  claim 1 , which comprises at least a portion of an adenovirus serotype 45 hexon protein in place of at least a portion of the endogenous serotype 28 hexon protein, and at least a portion of an adenovirus serotype 45 fiber protein in place of at least a portion of the endogenous serotype 28 fiber protein. 
     
     
         4 . The adenoviral vector of  claim 1 , wherein the portion of an adenovirus serotype 45 hexon protein comprises at least one hypervariable region (HVR). 
     
     
         5 . The adenoviral vector of  claim 4 , wherein the portion of an adenovirus serotype 45 hexon protein comprises nine HVRs. 
     
     
         6 . The adenoviral vector of  claim 1 , wherein the portion of an adenovirus serotype 45 hexon protein comprises the amino acid sequence of SEQ ID NO: 1, or an amino acid sequence that is at least 91.4% identical to SEQ ID NO: 1. 
     
     
         7 . The adenoviral vector of  claim 6 , wherein the portion of an adenovirus serotype 45 hexon protein is encoded by the nucleic acid sequence of SEQ ID NO: 2. 
     
     
         8 . The adenoviral vector of  claim 1 , wherein the portion of an adenovirus serotype 45 fiber protein comprises the amino acid sequence of SEQ ID NO: 3, or an amino acid sequence that is at least 67% identical to SEQ ID NO: 3. 
     
     
         9 . The adenoviral vector of  claim 8 , wherein the portion of an adenovirus serotype 45 fiber protein is encoded by the nucleic acid sequence of SEQ ID NO:
 4.   
     
     
         10 . The adenoviral vector of  claim 1 , which comprises:
 (a) an amino acid sequence of a serotype 28 adenovirus penton protein,   (b) an amino acid sequence of a serotype 28 adenovirus pIX protein,   (c) an amino acid sequence of a serotype 28 adenovirus p100 protein,   (d) an amino acid sequence of a serotype 28 adenovirus L1 52/55K protein, or   (e) any combination of (a)-(d).   
     
     
         11 . The adenoviral vector of  claim 1 , wherein the adenoviral vector requires complementation of a deficiency in one or more early regions of the adenoviral genome for propagation and does not require complementation of any other deficiency of the adenoviral genome for propagation. 
     
     
         12 . The adenoviral vector of  claim 1 , wherein the one or more early regions are selected from the group consisting of the E1 region, the E2 region, and the E4 region of the adenovirus genome. 
     
     
         13 . The adenoviral vector of  claim 12 , wherein the adenoviral vector requires complementation of a deficiency in the E1 region of the adenoviral genome for propagation and does not require complementation of any other deficiency of the adenoviral genome for propagation. 
     
     
         14 . The adenoviral vector of  claim 12 , wherein the adenoviral vector requires complementation of a deficiency in the E1A region or the E1B region of the adenoviral genome for propagation and does not require complementation of any other deficiency of the adenoviral genome for propagation. 
     
     
         15 . The adenoviral vector of  claim 12 , wherein the adenoviral vector requires at most complementation of a deficiency in the E4 region of the adenoviral genome for propagation and does not require complementation of any other deficiency of the adenoviral genome for propagation. 
     
     
         16 . The adenoviral vector of  claim 12 , wherein the adenoviral vector requires complementation of a deficiency in the E1 region of the adenoviral genome and a deficiency in the E4 region of the adenoviral genome for propagation and does not require complementation of any other deficiency of the adenoviral genome for propagation. 
     
     
         17 . The adenoviral vector of  claim 1 , which comprises the nucleic acid sequence of SEQ ID NO: 10. 
     
     
         18 . The adenoviral vector of  claim 1  further comprising a transgene. 
     
     
         19 . A composition comprising the adenoviral vector of  claim 1  and a pharmaceutically acceptable carrier.