Compositions and methods for flavivirus vaccination
Compositions of a recombinant adenovirus based vector vaccine containing one or more flavivirus antigen genes are disclosed herein. Methods for constructing and producing such vaccines and methods of using these vaccines to generate immune responses against flaviviruses are also described. Compositions described herein allow for vaccinations in subjects with preexisting immunity to adenovirus.
1. A cell comprising a composition, wherein the composition comprises:
a replication defective adenovirus vector comprising a deletion in an E1 gene region and a deletion in an E2b gene region; and
a sequence encoding a Zika virus target antigen.
2. The cell of claim 1 , wherein the sequence encoding a Zika virus target antigen comprises a sequence encoding a plurality of Zika virus target antigens.
3. The cell of claim 2 , wherein the sequence encoding a plurality of Zika virus target antigens comprises a plurality of gene inserts each corresponding to a target antigen, wherein each gene insert is separated by a nucleic acid sequence encoding a self-cleaving 2A peptide.
4. The cell of claim 3 , wherein the self-cleaving 2A peptide is derived from Porcine teschovirus-1 virus or Thosea asigna virus.
5. The cell of claim 1 , wherein the replication defective virus vector further comprises a deletion in an E3 gene region, an E4 gene region, or any combination thereof.
6. The cell of claim 1 , wherein the Zika virus target antigen comprises an antigen selected from the group consisting of C (capsid protein), E (envelope protein), prM (pre-membrane protein), M (membrane protein), NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5, or any combination thereof.
7. The cell of claim 1 , wherein the sequence encoding a Zika virus target antigen comprises an N-terminal GCCGCCACC sequence.
8. The cell of claim 1 , wherein the replication defective adenovirus vector further comprises a nucleic acid sequence encoding a protein that increases Zika virus target antigen immunogenicity.
9. The cell of claim 1 , wherein the composition or the replication defective adenovirus vector further comprises a nucleic acid sequence encoding a costimulatory molecule or an immunological fusion partner.
10. A pharmaceutical composition comprising the cell according to claim 1 and a pharmaceutically acceptable carrier.
11. The cell of claim 1 , wherein the cell is a dendritic cell (DC).
12. A method of preparing a vaccine, comprising preparing a pharmaceutical composition according to claim 10 .
13. A method of generating an immune response against a Zika virus target antigen in a subject, comprising: administering to the subject a composition comprising the Zika virus target antigen of claim 6 .
14. A method of preventing Zika virus infection in a subject, the method comprising administering to the subject a composition comprising:
a replication defective adenovirus vector comprising a deletion in an E2b gene region; and
a sequence encoding at least one Zika virus target antigen.
15. The method of claim 14 , wherein the subject has preexisting immunity to an adenovirus or adenovirus vector.
16. The method of claim 14 , wherein the administering of the composition to the subject comprises administering 1×10 9 to 5×10 12 virus particles per dose.