Vaccine Against Pandemic Strains Of Influenza Viruses
The present disclosure provides compositions and methods for eliciting an immune response against avian or pandemic influenza. The compositions include adenovirus vectors comprising avian influenza antigens, recombinant adenovirus and immunogenic compositions comprising such recombinant vectors and adenovirus. Methods for eliciting an immune response against avian or pandemic influenza involving administering such adenovirus vectors or recombinant adenovirus are also provided.
1 . A recombinant adenovirus vector comprising a polynucleotide sequence that encodes at least one antigen of an avian influenza strain.
2 . The recombinant adenovirus vector of claim 1 , wherein the polynucleotide sequence encodes an avian influenza HA antigen.
3 . The recombinant adenovirus vector of claim 2 , wherein the polynucleotide sequence encodes a plurality of avian influenza HA antigens.
4 . The recombinant adenovirus vector of claim 3 , wherein the polynucleotide sequence encodes a plurality of variants of the same HA antigen subtype.
5 . The recombinant adenovirus vector of claim 3 , wherein the polynucleotide sequence encodes a plurality of HA antigens of different HA subtypes.
6 . The recombinant adenovirus vector of claim 1 , wherein the at least one polynucleotide sequence encodes an avian influenza NA antigen.
7 . The recombinant adenovirus vector of claim 1 , wherein the avian influenza antigen is an H 5 N 1 strain antigen, an H 7 N 7 strain antigen, or an H 9 N 2 strain antigen.
8 . The recombinant adenovirus vector of claim 1 , wherein the polynucleotide sequence encodes a plurality of influenza antigens.
9 . The recombinant adenovirus vector of claim 8 , wherein the polynucleotide sequence encodes at least one influenza internal protein.
10 . The recombinant adenovirus vector of claim 9 , wherein the influenza internal protein is and M1 protein, an M2 protein, an NP protein, ma PB1 protein, a PB2 protein, and NS1 protein, and NS2 protein, or a combination thereof.
11 . The recombinant adenovirus vector of claim 9 , wherein the influenza internal protein is an M1 protein, an M2 protein, an NP protein, or a combination of two or more thereof.
12 . The recombinant adenovirus vector of claim 9 , wherein the internal protein is of a non-avian influenza strain.
13 . The recombinant adenovirus vector of claim 9 , wherein the internal protein is of an H1N1, H2N2 or H3N2 influenza strain.
14 . The recombinant adenovirus vector of claim 1 , wherein the adenovirus vector is a human adenovirus vector.
15 . The recombinant adenovirus vector of claim 1 , wherein the adenovirus vector is a non-human adenovirus vector.
16 . The recombinant adenovirus vector of claim 15 , wherein the non-human adenovirus vector is a porcine adenovirus vector, a bovine adenovirus vector, a canine adenovirus vector, a murine adenovirus vector, an ovine adenovirus vector, an avian adenovirus vector or a simian adenovirus vector.
17 . The recombinant adenovirus vector of claim 1 , wherein the adenovirus vector is a replication defective adenovirus vector.
18 . The recombinant adenovirus vector of claim 17 , wherein the replication defective adenovirus comprises a mutation in at least one of an E I region gene and an E3 region gene.
19 . The recombinant adenovirus vector of claim 1 , wherein the adenovirus vector comprises a replication defective human adenovirus vector comprising a polynucleotide sequence that encodes an HA, an NA antigen, or both an HA antigen and an NA antigen of an avian influenza strain and an M1 protein, an M2 protein, an NP protein, or a combination of two or more of an M1 protein, an M2 protein and an NP protein of a second strain of influenza.
20 . The recombinant adenovirus vector of claim 1 , wherein the adenovirus vector comprises a replication defective porcine or bovine adenovirus vector comprising a polynucleotide sequence that encodes an HA, an NA antigen, or both an HA antigen and an NA antigen of an avian influenza strain an M1 protein, an M2 protein, an NP protein, or a combination of two or more of an M1 protein, an M2 protein and an NP protein of a second strain of influenza.
21 . A recombinant adenovirus comprising the adenovirus vector of claim 1 .
22 - 34 . (canceled)
35 . An immunogenic composition comprising:
the recombinant adenovirus vector of claim 1 and
a pharmaceutically acceptable carrier.
36 - 38 . (canceled)
39 . An isolated cell comprising one or more heterologous nucleic acids, which one or more heterologous nucleic acids comprises a first polynucleotide sequence that encodes at least a first adenovirus E protein and a second polynucleotide sequence that encodes at least a second adenovirus E protein, wherein the first and second adenovirus E proteins are selected from different adenovirus strains, and
wherein the cell supports the growth of a plurality of strains of replication deficient human and/or non-human adenoviruses.
40 . The cell line of claim 39 , wherein the at least first adenovirus E protein and the at least second adenovirus E protein are both E1 proteins.
41 . The cell line of claim 39 , wherein the at least first and second adenovirus E proteins are from different adenovirus strains with different species tropism.
42 . The cell line of claim 41 , wherein the at least first adenovirus E protein comprises one or more human adenovirus E proteins, and wherein the at least second adenovirus E protein comprises one or more non-human adenovirus E proteins.
43 . The cell line of claim 42 , wherein the at least second adenovirus E protein comprises one or more bovine E proteins.
44 . The cell line of claim 43 , comprising a plurality of human E1 proteins and a plurality of bovine E1 proteins.
45 . The cell line of claim 42 , wherein the at least second adenovirus E protein comprises one or more porcine E proteins.
46 . The cell line of claim 45 , comprising a plurality of human E1 proteins and a plurality of porcine E1 proteins.
47 . A method of producing an immune response against at least one avian or pandemic strain of influenza in a subject, the method comprising:
administering to a subject an immunogenic composition_comprising at least one of:
a recombinant adenovirus vector comprising a polynucleotide that encodes at least one antigen of an avian influenza strain; and,
a recombinant adenovirus comprising at least one antigen of an avian influenza strain.
48 . The method of claim 47 , wherein the immune response is a protective or partially protective immune response against one or more avian or pandemic strains of influenza.
49 . The method of claim 48 , wherein the immune response is protective or partially protective against a plurality of avian or pandemic strains of influenza.
50 . The method of claim 47 , wherein the immune response comprises the production of neutralizing antibodies that bind an antigen of at least one avian or pandemic strain of influenza.
51 . The method of claim 47 , wherein the immune response comprises the production of neutralizing antibodies that bind antigens of a plurality of avian or pandemic strains of influenza.
52 . The method of claim 47 , wherein the immune response further comprises a T cell response specific for at least one influenza internal protein.
53 . The method of claim 52 , wherein the at least one internal protein is an M1 protein, an M2 protein, an NP protein, or a combination thereof.
54 . The method of claim 53 , wherein the T cell response is specific for an epitope of the influenza internal protein that is conserved among a plurality of influenza strains.
55 . The method of claim 54 , wherein the plurality of influenza strains are of more than one serotype.
56 . The method of claim 47 , comprising administering the immunogenic composition intranasally, orally, ocularly, intravenously, intramuscularly, transdermally, intradermally, or subcutaneously.
57 . The method of claim 47 , wherein the subject is a human subject.
58 . The method of claim 47 , wherein the subject is a non-human mammal.
59 . The method of claim 47 , wherein the subject is a bird.
60 . The method of claim 59 , wherein the subject is a domesticated fowl.
61 . The method of claim 60 , comprising administering the immunogenic composition in ovo to an embryonated egg.
62 . The method of claim 60 , comprising administering the immunogenic composition in a spray or controlled droplet to a plurality of birds in a common airspace.
63 . The method of claim 60 , comprising administering the immunogenic composition in drinking water.
64 . The method of claim 47 , comprising administering an adenovirus vector with a polynucleotide sequence that encodes a plurality of influenza antigens or an adenovirus comprising a plurality of influenza antigens.
65 . The method of claim 64 , wherein the plurality of antigens comprises an HA antigen, an NA antigen or both an HA antigen and an NA antigen of an avian influenza strain
66 . The method of claim 64 , wherein the plurality of antigens comprises variants of the same HA antigen subtype.
67 . The method of claim 64 , wherein the plurality of antigens comprises a plurality of HA antigens from different avian influenza subtypes.
68 . The method of claim 64 , wherein the plurality of antigens comprises at least one avian influenza HA antigen and at least one influenza internal protein.
69 . The method of claim 68 , wherein the influenza internal protein is an M1 protein, an M2 protein, an NP protein, or a combination of two or more thereof.
70 . A method of producing a recombinant avian influenza virus antigen, the method comprising:
replicating in a cell an adenovirus comprising at least one polynucleotide sequence that encodes an avian influenza antigen.
71 . The method of claim 70 , comprising replicating the adenovirus by introducing a replication defective adenovirus vector into a cell capable of supporting replication of the replication defective vector.
72 . The method of claim 71 , wherein the cell is a multifunctional cell that expresses at least two different E proteins, wherein the different E proteins are of at least two different strains of adenovirus with different species tropism.
73 . The method of claim 70 , wherein the avian influenza antigen is at least one of an HA antigen or an NA antigen.
74 . The method of claim 73 , wherein the antigen is selected from an H5, an H7 or an H9 strain of influenza.
75 . The method of claim 70 , wherein the at least one polynucleotide sequence encodes a plurality of influenza antigens.