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HIV DNA VACCINE REGULATED BY A CAEV-DERIVED PROMOTER

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  • Publication Date:
    August 16, 2012
  • معلومة اضافية
    • Document Number:
      20120207782
    • Appl. No:
      13/185164
    • Application Filed:
      July 18, 2011
    • نبذة مختصرة :
      The present invention is directed to a DNA vaccine for immunization against HIV. The invention comprises a DNA molecule that has a sequence encoding a plurality of viral proteins capable of stimulating an immune response against HIV. The DNA molecule is rendered safe for use as a vaccine by the disruption of genes encoding reverse transcriptase, integrase, and Vif. The DNA molecule is further rendered safe by at least a partial deletion of the 3′ LTR.
    • Inventors:
      Narayan, Opendra (Lenexa, KS, US); Narayan, Euan (Lenexa, KS, US); Chebloune, Yahia (Grenoble, FR)
    • Assignees:
      University of Kansas Medical Center (Kansas City, KS, US), National Institute for Agriculture Research (Paris Cedex 07, FR)
    • Claim:
      1. A DNA composition capable of stimulating an immune response comprising: a promoter sequence derived from Caprine Arthritis Encephalitis Goat Lentivirus (CAEV) operably linked to a coding sequence, wherein the coding sequence encodes a gag gene of Human Immunodeficiency Virus (HIV), a pro gene of HIV, a vpx gene of Simian Immunodeficiency Virus (SIV), a vpr gene of SIV, a vpu gene of HIV, a nef gene of HIV, a tat gene of HIV, an env gene of HIV, and a rev gene of HIV, with the coding sequence operably linked to a polyadenylation sequence, and wherein the DNA composition does not include functional reverse transcriptase (rt), integrase (int), and viral infectivity factor (vif) genes.
    • Claim:
      2. The DNA composition of claim 1, wherein the coding sequence encodes at least one non-functional gene.
    • Claim:
      3. The DNA composition of claim 1, wherein the polyadenylation sequence is an SV40 polyadenylation sequence.
    • Claim:
      4. The DNA composition of claim 1, wherein the DNA composition is in a pharmaceutically acceptable carrier.
    • Claim:
      5. A pharmaceutical composition comprising: (a) a DNA composition having a promoter sequence derived from Caprine Arthritis Encephalitis Goat Lentivirus (CAEV) operably linked to a coding sequence, wherein the coding sequence encodes a gag gene of Human Immunodeficiency Virus (HIV), a pro gene of HIV, a vpx gene of Simian Immunodeficiency Virus (SIV), a vpr gene of SIV, a vpu gene of HIV, a nef gene of HIV, a tat gene of HIV, an env gene of HIV, and a rev gene of HIV, with the coding sequence operably linked to a polyadenylation sequence, and wherein the DNA composition does not include functional reverse transcriptase (rt), integrase (int), and viral infectivity factor (vif) genes; and, (b) a pharmaceutically acceptable carrier.
    • Claim:
      6. The pharmaceutical composition of claim 5, wherein the coding sequence encodes at least one non-functional gene.
    • Claim:
      7. The pharmaceutical composition of claim 5, wherein the promoter sequence is a 5′ long terminal repeat (LTR) of SIV.
    • Claim:
      8. The pharmaceutical composition of claim 5, wherein the DNA composition lacks a functional 3′ LTR sequence.
    • Claim:
      9. The pharmaceutical composition of claim 5, wherein the polyadenylation sequence is an SV40 polyadenylation sequence.
    • Claim:
      10. A method of stimulating an immune response in a recipient against Human Immunodeficiency Virus (HIV) comprising: administering to the recipient a DNA composition comprising a promoter sequence derived from Caprine Arthritis Encephalitis Goat Lentivirus (CAEV) operably linked to a coding sequence, wherein the coding sequence encodes a gag gene of Human Immunodeficiency Virus (HIV), a pro gene of HIV, a vpx gene of Simian Immunodeficiency Virus (SIV), a vpr gene of SIV, a vpu gene of HIV, a nef gene of HIV, a tat gene of HIV, an env gene of HIV, and a rev gene of HIV, with the coding sequence operably linked to a polyadenylation sequence, and wherein the DNA composition does not include functional reverse transcriptase (rt), integrase (int), and viral infectivity factor (vif) genes.
    • Claim:
      11. The method of claim 10, wherein the coding sequence encodes at least one non-functional gene.
    • Claim:
      12. The method of claim 10, wherein the promoter sequence is a 5′ long terminal repeat (LTR) of SIV.
    • Claim:
      13. The method of claim 10, wherein the polyadenylation sequence is an SV40 polyadenylation sequence.
    • Claim:
      14. The method of claim 10, wherein the DNA composition is in a pharmaceutically acceptable carrier.
    • Claim:
      15. The method of claim 10 further comprising administering to the recipient at least one cytokine.
    • Claim:
      16. The method of claim 10, further comprising administering to the recipient at least one anti-viral drug therapy.
    • Claim:
      17. A method of treating an HIV positive recipient comprising: administering to the recipient a DNA composition comprising a promoter sequence derived from Caprine Arthritis Encephalitis Goat Lentivirus (CAEV) operably linked to a coding sequence, wherein the coding sequence encodes a gag gene of Human Immunodeficiency Virus (HIV), a pro gene of HIV, a vpx gene of Simian Immunodeficiency Virus (SIV), a vpr gene of SIV, a vpu gene of HIV, a nef gene of HIV, a tat gene of HIV, an env gene of HIV, and a rev gene of HIV, with the coding sequence operably linked to a polyadenylation sequence, and wherein the DNA composition does not include functional reverse transcriptase (rt), integrase (int), and viral infectivity factor (vif) genes.
    • Claim:
      18. The method of claim 17, wherein the coding sequence encodes at least one non-functional gene.
    • Claim:
      19. The method of claim 17, wherein the promoter sequence is a 5′ long terminal repeat (LTR) of SIV.
    • Claim:
      20. The method of claim 17, wherein the polyadenylation sequence is an SV40 polyadenylation sequence.
    • Claim:
      21. The method of claim 17, wherein the DNA composition is in a pharmaceutically acceptable carrier.
    • Claim:
      22. The method of claim 17 further comprising administering to the recipient at least one cytokine.
    • Claim:
      23. The method of claim 17, further comprising administering to the recipient at least one anti-viral drug therapy.
    • Claim:
      24. A method of vaccinating a recipient against HIV comprising: administering to the recipient a DNA composition comprising a promoter sequence derived from Caprine Arthritis Encephalitis Goat Lentivirus (CAEV) operably linked to a coding sequence, wherein the coding sequence encodes a gag gene of Human Immunodeficiency Virus (HIV), a pro gene of HIV, a vpx gene of Simian Immunodeficiency Virus (SIV), a vpr gene of SIV, a vpu gene of HIV, a nef gene of HIV, a tat gene of HIV, an env gene of HIV, and a rev gene of HIV, with the coding sequence operably linked to a polyadenylation sequence, and wherein the DNA composition does not include functional reverse transcriptase (rt), integrase (int), and viral infectivity factor (vif) genes.
    • Claim:
      25. The method of claim 24, wherein the coding sequence encodes at least one non-functional gene.
    • Claim:
      26. The method of claim 24, wherein the promoter sequence is a 5′ long terminal repeat (LTR) of SIV.
    • Claim:
      27. The method of claim 24, wherein the polyadenylation sequence is an SV40 polyadenylation sequence.
    • Claim:
      28. The method of claim 24, wherein the DNA composition is in a pharmaceutically acceptable carrier.
    • Claim:
      29. The method of claim 24 further comprising administering to the recipient at least one cytokine.
    • Claim:
      30. The method of claim 24 further comprising administering to the recipient at least one anti-viral drug therapy.
    • Current U.S. Class:
      4242/021
    • Current International Class:
      61; 61; 12
    • الرقم المعرف:
      edspap.20120207782