Human adenovirus serotype 5 vectors containing E1 and E2B deletions encoding the ebola virus glycoprotein
Methods for generating immune responses to Ebola virus antigens 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 composition comprising an adenovirus 5 vector comprising a nucleotide sequence encoding a first antigen, wherein the first antigen is a glycoprotein (GP), wherein the adenovirus 5 vector comprises a deletion in an E1 gene region and a deletion in an E2b gene region, and wherein the GP is from an Ebola selected from the group consisting of Zaire ebolavirus (EBOV), Sudan virus (SUDV), Tai Forest ebolavirus (TAFV), Bundibugyo ebolavirus (BDBV), Reston virus (RESTV), and any combination thereof.
2. The composition of claim 1 , wherein the adenovirus 5 vector further comprises a deletion in an E3 gene region, an E4 gene region, or any combination thereof.
3. The composition of claim 1 , wherein the adenovirus 5 vector is a replication defective adenovirus 5 vector.
4. The composition of claim 1 , further comprising an immunogenic component, wherein the immunogenic component comprises a cytokine selected from the group consisting of IFN-γ, TNFα IL-2, IL-8, IL-12, IL-18, IL-7, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13.
5. The composition of claim 4 , wherein the immunogenic component is IL-7.
6. The composition of claim 3 , wherein the replication defective adenovirus vector is capable of generating an immune response to the GP following one round, two rounds, or multiple rounds of immunization with the same type of replication defective adenovirus vector.
7. The composition of claim 1 , wherein the adenovirus 5 vector is capable of inducing an immune response against cells expressing the Ebola virus antigen in a human that is at least 2 fold over basal, as measured as an Ebola virus antigen specific antibody response, as a neutralizing Ebola virus antigen specific antibody response, as Ebola virus antigen specific cell-mediated immunity (CMI), as Ebola virus antigen specific IFN-γ secretion, as Ebola virus antigen specific IL-2 secretion, by ELISpot assay, or by any combination thereof.
8. The composition of claim 7 , wherein the immune response is measured as an Ebola virus antigen specific antibody response.
9. The composition of claim 1 , further comprising a nucleotide encoding an immunological fusion partner.
10. The composition of claim 8 , wherein the immunological fusion partner comprises a Mycobacterium tuberculosis -derived Ra12 fragment, protein D fragment, NS1, or LYTA.
11. The composition of claim 1 , wherein the adenovirus 5 vector comprises a nucleotide encoding a second antigen.
12. The composition of claim 11 , wherein the adenovirus 5 vector comprises a nucleotide encoding a third antigen.
13. The composition of claim 11 , wherein the second antigen is selected from NP, VP40, VP35, VP30, VP24, and L.
14. The composition of claim 12 , wherein the third antigen is selected from NP, VP40, VP35, VP30, VP24, and L.
15. The composition of claim 1 in a single dose form comprising 5.0×10 11 virus particles (VPs).
16. A method of generating an immune response against an Ebola virus antigen in a human comprising:
(a) a first phase of treatment comprising administering to the human a first composition comprising the composition of claim 1 ; and
(b) a subsequent second phase of treatment comprising administering to the human a second composition comprising a second replication defective adenovirus vector encoding an Ebola virus antigen that induces an immune response against cells expressing the Ebola virus antigen in the human.
17. The method of claim 16 , wherein the first phase is at least 2 weeks.
18. The method of claim 16 , wherein the second phase is at least 2 months.
19. The method of claim 16 , wherein the second phase starts 3-16 weeks after first phase ends.
20. The method of claim 16 , wherein in the first phase two administrations of the composition are at least 18 days apart.
21. The method of claim 20 , wherein in the first phase two administrations of the composition are about 21 days apart.
22. The method of claim 20 , wherein in the first phase two administrations of the composition are at most 24 days apart.
23. The method of claim 16 , wherein in the second phase two administrations of the replication defective adenovirus are at least 10 weeks apart.
24. The method of claim 23 , wherein in the second phase two administrations of the replication defective adenovirus are about 13 weeks apart.
25. The method of claim 23 , wherein in the second phase two administrations of the replication defective adenovirus are at most 16 weeks apart.