Adenoviral-based vectors

Abstract

The present invention provides replication competent adenoviral vectors capable of expressing antigens from infectious pathogens, such as influenza virus. The adenoviral vectors can be used to vaccinate subjects against the infectious pathogens. The adenoviral vectors comprise heterologous sequences encoding the antigens. The heterologous sequences can be inserted into various locations in the adenoviral vectors, including in or near specific E3 deletions and/or integrated into the adenoviral hexon coding region. The adenoviral vectors can be derived from any adenoviral serotype, particularly an Ad4 or Ad7 serotype.

1 . A vaccine comprising an adenoviral vector comprising a first heterologous sequence, wherein said adenoviral vector is replication competent and has a partial E3 deletion, and wherein the first heterologous sequence is integrated into a location containing the partial E3 deletion. 
     
     
         2 . The vaccine of  claim 1 , wherein the adenoviral vector is derived from Ad2, Ad3, Ad4, Ad5, Ad6, Ad7, Ad11, Ad20, Ad21, Ad22, Ad23, Ad24, Ad25, Ad26, Ad28, Ad34, Ad35, Ad40, Ad41, Ad48, Ad49, or Ad50. 
     
     
         3 . (canceled) 
     
     
         4 . The vaccine of  claim 1 , wherein the partial E3 deletion comprises deletion of at least 1, 2 or 3 open reading frames within the E3 region. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The vaccine of  claim 1 , wherein the adenoviral vector is derived from Ad4 and the partial E3 deletion comprises a deletion of E3 24.8 k, E3 6.3 k, and E3 29.7 k. 
     
     
         8 . The vaccine of  claim 1 , wherein the adenoviral vector is derived from Ad7 and the partial E3 deletion comprises a deletion of E3 20.1 k, E3 20.6 k, and E3 7.7 k. 
     
     
         9 . (canceled) 
     
     
         10 . The vaccine of  claim 1 , wherein the expression of the first heterologous sequence is under the control of an endogenous adenoviral promoter. 
     
     
         11 . The vaccine of  claim 10 , wherein the expression of the first heterologous sequence is under the control of endogenous Major Late Promoter and tripartite leader. 
     
     
         12 . The vaccine of  claim 1 , wherein the expression of the first heterologous sequence is under the control of a non-adenoviral promoter. 
     
     
         13 . The vaccine of  claim 12 , wherein the expression of the first heterologous sequence is under the control of a cytomegalovirus (CMV) promoter. 
     
     
         14 . The vaccine of  claim 12 , wherein the expression of the first heterologous sequence is under the control of a CMV promoter and an adenoviral tripartite leader. 
     
     
         15 . The vaccine of  claim 1 , wherein the first heterologous sequence is operably linked to an adenoviral splice acceptor. 
     
     
         16 . The vaccine of  claim 15 , wherein the first heterologous sequence is operably linked to a native E3 24.8 k splice acceptor. 
     
     
         17 . The vaccine of  claim 1 , wherein the first heterologous sequence is operably linked to an adenoviral polyA signal sequence. 
     
     
         18 . (canceled) 
     
     
         19 . The vaccine of  claim 1 , wherein the first heterologous sequence encodes an immunogenic protein of an infectious pathogen. 
     
     
         20 . The vaccine of  claim 19 , wherein the infectious pathogen is selected from the group consisting of a virus, a  bacterium,  a protist, and a fungus. 
     
     
         21 . The vaccine of  claim 20 , wherein the infectious pathogen is influenza, human immunodeficiency virus, or human papilloma virus. 
     
     
         22 . The vaccine of  claim 20 , wherein the infectious pathogen is  Bacillus, Shigella, Mycobacterium,  or  Plasmodium.    
     
     
         23 . The vaccine of  claim 1 , wherein the first heterologous sequence encodes influenza hemaglutinin, influenza neuraminidase, influenza M2, a multimer of M2e, a multimer of HTL epitopes, or a multimer of CTL epitopes. 
     
     
         24 - 28 . (canceled) 
     
     
         29 . A vaccine comprising an adenoviral vector comprising a first heterologous sequence, wherein said adenoviral vector is derived from Ad2, Ad3, Ad4, Ad5, Ad6, Ad7, Ad11, Ad20, Ad21, Ad22, Ad23, Ad24, Ad25, Ad26, Ad28, Ad34, Ad35, Ad40, Ad41, Ad48, Ad49, Ad50, Ad C1, Ad C3, Ad C6, Ad C7, or Ad68, is replication competent, and has a full E3 deletion. 
     
     
         30 - 51 . (canceled) 
     
     
         52 . The vaccine of  claim 1 , which is formulated for oral, intranasal, sublingual, intravesical, rectal, or intravaginal administration. 
     
     
         53 . A vaccine of  claim 1 , further comprising an acceptable carrier. 
     
     
         54 . A dosage unit of the vaccine of  claim 1 , wherein a single dose comprises about 10 3  to about 10 13  adenoviral particles. 
     
     
         55 . A method of inducing an immune response to an infectious pathogen in a subject comprising administering to the subject the vaccine of  claim 1 . 
     
     
         56 . (canceled) 
     
     
         57 . The method of  claim 55 , wherein the infectious pathogen is influenza, HIV, HPV,  Bacillus, Plasmodium,  Mycobacteria, or  Shigella.    
     
     
         58 . The method of  claim 55 , wherein the subject has an infection induced by said infectious pathogen.