Sequential administration of a replication defective adenovirus vector in vaccination protocols
View Patent ↗Methods for generating immune responses using adenovirus vectors that allow multiple vaccinations with the same adenovirus vector and vaccinations in individuals with preexisting immunity to adenovirus are provided.
1. A method of generating an immune response against one or more target antigens in an individual comprising:
(a) administering to the individual a first vector comprising: i) a replication defective adenovirus vector, wherein said adenovirus vector has a deletion in the E2b region, and ii) a nucleic acid encoding a first target antigen;
(b) subsequently administering to the individual a second vector comprising: i) the replication defective adenovirus vector of step (a), and ii) a nucleic acid encoding a second target antigen, wherein the second target antigen of the second vector is the same or different from the first target antigen of the first vector;
thereby generating an immune response against the first target antigen and the second target antigen.
2. The method of claim 1 , wherein the first and second vectors are not gutted vectors.
3. The method of claim 1 , wherein the individual has preexisting immunity to an adenovirus.
4. The method of claim 1 , wherein the first and second target antigens of the first and the second vectors are derived from the same infectious organism.
5. The method of claim 1 , wherein the first and second target antigens of the first and the second vectors are derived from different infectious organisms.
6. The method of claim 1 , wherein the first target antigen of the first vector comprises an HIV protein, or a variant or fragment thereof.
7. The method of claim 6 , wherein the second target antigen of the second vector comprises an E. coli β-galactosidase.
8. The method of claim 6 , wherein the HIV protein is an HIV-gag protein.
9. The method of claim 1 , wherein the first target antigen of the first vector comprises an HIV protein, or a variant or fragment thereof, and the second target antigen of the second adenovirus vector comprises an HIV protein, or a variant or fragment thereof.
10. The method of claim 9 , wherein the first target antigen of the first vector comprises an HIV protein, or a variant or fragment thereof, and the second target antigen of the second adenovirus vector comprises an HIV protein, or a variant or fragment thereof, that is different from the HIV protein of the first adenovirus vector.
11. The method of claim 1 , wherein the first target antigen of the first vector comprises a cancer protein, or a variant or fragment thereof.
12. The method of claim 11 , wherein the first target antigen of the first vector comprises a Her2/neu antigen, or a variant or fragment thereof.
13. The method of claim 11 , wherein the first target antigen of the first vector comprises a carcinoembryonic protein, or a variant or fragment thereof.
14. The method of claim 1 , wherein the first target antigen of the first vector comprises a human papillomavirus protein, or a variant or fragment thereof.
15. The method of claim 14 , wherein the human papillomavirus protein is viral protein E6.
16. The method of claim 14 , wherein the human papillomavirus protein is viral protein E7.
17. The method of claim 1 , wherein the first target antigen of the first vector comprises an antigen selected from the group consisting of: a bacterial antigen, a viral antigen, an antigen derived from a protozoan protein, an antigen derived from a fungal protein, an antigen derived from a mold protein, an antigen derived from a mammalian protein, and an antigen derived from an avian protein, or a variant or fragment thereof.
18. The method of claim 1 , wherein the first target antigen of the first vector comprises an antigen derived from a virus selected from the group consisting of: a Venezuelan Equine Encephalitis Virus (VEEV), a Western Equine Encephalitis Virus, and a Japanese Encephalitis Virus, or a variant or fragment thereof.
19. The method of claim 1 , wherein the first target antigen of the first vector comprises a Leishmania protein.
20. The method of claim 1 , wherein the first target antigen of the first vector comprises a cancer protein selected from the group consisting of:
carcinoembryonic antigen, Her2/Neu, a human papilloma virus protein and WT-1, or a variant or fragment thereof.
21. The method of claim 20 , wherein the variant or fragment is not oncogenic or has reduced oncogenicity compared to the wild type cancer protein.
22. The method of claim 1 , wherein the first target antigen of the first vector comprises an influenza virus protein, or a fragment or variant thereof.
23. The method of claim 22 , wherein the influenza virus protein is derived from an influenza virus selected from the group consisting of: H5N1, H3N2, H9N1, H1N1, H2N2, H7N7, H1N2, H9N2, H7N2, H7N3, and H10N7.
24. The method of claim 22 , wherein the influenza virus protein is selected from the group consisting of: haemagglutinin, neuraminidase, and matrix protein M1.
25. The method of claim 1 , wherein the first vector is not a gutted vector.
26. The method of claim 1 , wherein the second vector is not a gutted vector.