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CA-3030447-C - COMPOSITIONS AND METHODS FOR FLAVIVIRUS VACCINATION

CA3030447CCA 3030447 CCA3030447 CCA 3030447CCA-3030447-C

Abstract

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 flavivirus are also described. Compositions described herein allow for vaccinations in subjects with preexisting immunity to adenovirus.

Inventors

  • Frank R. Jones
  • Joseph Balint
  • Adrian Rice
  • Yvette Latchman
  • Elizabeth Gabitzsch

Assignees

  • ETUBICS CORPORATION

Dates

Publication Date
20260505
Application Date
20170714
Priority Date
20160715

Claims (20)

  1. CLAIMS WHAT IS CLAIMED IS: 1. A composition comprising: a replication defective adenovirus 5 (Ad5) vector comprising a deletion of the E2b gene region and a deletion of the E1 gene region; and a nucleic acid sequence encoding a zika virus target antigen, wherein the target antigen is a wild type envelope antigen, and wherein the nucleic acid sequence has at least 85% identity to SEQ ID NO: 26.
  2. 2. The composition of claim 1, wherein the replication defective virus vector comprises a deletion in an E3 gene region.
  3. 3. The composition of claim 2, wherein the deletion in the E3 gene region comprises at least one base pair.
  4. 4. The composition of claim 2 or 3, wherein the deletion in the E3 gene region results from a translocation of two or more base pairs.
  5. 5. The composition of claim 2, 3, or 4, wherein the deletion in the E3 gene region comprises at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, or at least 150 base pairs.
  6. 6. The composition of any one of claims 2 to 5, wherein the deletion in the E3 gene region comprises more than 150, more than 160, more than 170, more than 180, more than 190, more than 200, more than 250, or more than 300 base pairs.
  7. 7. The composition of any one of claims 1 to 6, wherein the replication defective virus vector comprises a deletion in an E4 gene region.
  8. 8. The composition of claim 7, wherein the deletion in the E4 gene region comprises at least one base pair.
  9. 9. The composition of claim 7 or 8, wherein the deletion in the E4 gene region results from a translocation of two or more base pairs. 170
  10. 10. The composition of claim 7, 8, or 9, wherein the deletion in the E4 gene region comprises at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, or at least 150 base pairs.
  11. 11. The composition of any one of claims 7 to 10, wherein the deletion in the E4 gene region comprises more than 150, more than 160, more than 170, more than 180, more than 190, more than 200, more than 250, or more than 300 base pairs.
  12. 12. The composition of any one of claims 1 to 11, wherein the sequence encoding the zika virus target antigen comprises at least 95% sequence identity to SEQ ID NO: 26.
  13. 13. The composition of any one of claims 1 to 11, wherein the nucleic sequence encoding the zika virus target antigen comprises at least 99% sequence identity to SEQ ID NO: 26.
  14. 14. The composition of any one of claims 1 to 13, wherein the replication defective Ad5 vector further comprises an element to increase the expression of the zika virus target antigen.
  15. 15. The composition of claim 14, wherein the element comprises at least one element, at least 2 elements, at least 3 elements, at least 4 elements, or at least 5 elements.
  16. 16. The composition of claim 14 or 15, wherein the element comprises an internal ribosome binding site.
  17. 17. The composition of claim 14, 15, or 16, wherein the element comprises a constitutive promoter.
  18. 18. The composition of any one of claims 14 to 17, wherein the element comprises an inducible promoter.
  19. 19. The composition of any one of claims 14 to 18, wherein the element comprises a transcription enhancer.
  20. 20. The composition of claim 19, wherein the transcription enhancer is a Rous sarcoma virus (RSV) enhancer.

Description

(Page 12 of 1639) COMPOSITIONS AND METHODS FOR FLA VIVIRUS VACCINATION [0001] <deleted> SEQUENCE LISTING [0002) This application contains a sequence listing in electronic form in ASCII text format. A copy of the sequence listing is available from the Canadian Intellectual Property Office. BACKGROUND [0003] Vaccines help the body fight disease by training the immune system to recognize and destroy harmful substances and diseased cells. Vaccines can be largely grouped into two types, preventive and treatment vaccines. Preventive vaccines are given to healthy people to prevent the development of specific diseases, while treatment vaccines, also referred to as immunotherapies, are given to a person who has been diagnosed with disease to help stop the disease from growing and spreading or as a preventive measure. [0004] Viral vaccines are currently being developed to help fight infectious diseases and cancers. These viral vaccines work by inducing expression of a small fraction of genes associated with a disease within the host's cells, which in tum, enhance the ability of the host's immune system to identify and destroy diseased cells. As such, clinical response of a viral vaccine can depend on the ability of the vaccine to obtain a high-level of immunogenicity and have sustained long-term expression. [0005] Therefore, there remains a need to discover novel compositions and methods for enhanced therapeutic response to complex diseases and especially to newly emerging disease threats. SUMMARY [0006) In various aspects, the present disclosure provides a composition comprising: a replication defective virus vector comprising a deletion in an E2b gene region; and a sequence encoding a flavivirus target antigen. In some aspects, the sequence encoding a flavivirus target antigen comprises a sequence encoding a plurality of flavivirus target antigens. In further aspects, the sequence encoding a plurality of flavivirus 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. In some aspects, the self-cleaving 2A peptide is derived from 1 (Page 23 of 1639) WO 2018/014006 PCT/US2017 /042269 Porcine teschovirus-1 virus or Thosea asigna virus. In some aspects, the plurality of flavivirus target antigens comprises three flavivirus target antigens or four flavivirus target antigens. [0007] In some aspects, the replication defective virus vector is an adenovirus vector. In further aspects, the replication defective virus vector is an adenovirus 5 (Ad5) vector. In still further aspects, the replication defective virus vector comprises a deletion in an E 1 gene region, an E3 gene region, an E4 gene region, or any combination thereo£ In some aspects, the deletion in the E2b gene region comprises a plurality of deletions in the E2b gene region. [0008) In some aspects, the deletion in the E2b gene region, the deletion in the El gene region, the deletion in the E3 gene region, the deletion in the E4 gene region, or any combination thereof, each comprises at least one base pair comprises. [0009] In other aspects, the deletion in the E2b gene region, the deletion in the El gene region, the deletion in the E3 gene region, the deletion in the E4 gene region, or any combination thereof results from a translocation of two or more base pairs. In some aspects, the deletion in the E2b gene region, the deletion in the El gene region, the deletion in the E3 gene region, the deletion in the E4 gene region, or any combination thereof each comprises at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, or at least 150 base pairs. In other aspects, the deletion in the E2b gene region, the deletion in the El gene region, the deletion in the E3 gene region, the deletion in the E4 gene region, or any combination thereof each comprises more than 150, more than 160, more than 170, more than 180, more than 190, more than 200, more than 250, or more than 300 base pairs. (0010] In some aspects, the flavivirus target antigen comprises an antigen of a virus selected from a group consisting of yellow fever virus (YFV), Japanese encephalitis virus (JEV), Tick-borne encephalitis virus (TBEV), Dengue virus (DENY), West Nile virus (WNV), zi.ka virus (ZIKA V), or any combination thereof In further aspects, the flavivirus target antigen comprises an antigen of a virus selected from the group consisting ofYFV, ZIKA V, or both. (0011) In still further aspects, the flavivirus target antigen comprises an antigen of ZIKA V. In some aspects, the flavivirus target antigen comprises an antigen selected from the group consisting of C (capsid protein), E (envelope protein), prM (pre-membrane protein), M (membrane protein), NSI, NS2A, NS2B, NS3, NS4A, NS4B, and NS5, or any combination thereof In some aspects, the flaviv