MVA expressing modified HIV envelope, GAG, and POL genes

Abstract

The invention provides modified virus Ankara (MVA), a replication-deficient strain of vaccinia virus, expressing human immunodeficiency virus (HIV) env, gag, and pol genes.

1 . A pharmaceutical composition comprising a recombinant MVA virus expressing an HIV env, gag, and pol gene or modified gene thereof for production of an HIV Env, Gag, and Pol antigen by expression from said recombinant MVA virus, wherein said HIV env gene is modified to encode an HIV Env protein composed of gp120 and the membrane-spanning and ectodomain of gp41 but lacking part or all of the cytoplasmic domain of gp41, and a pharmaceutically acceptable carrier, wherein said HIV env, gag, and pol genes are isolatable from an individual infected with Ugandan clade D isolate 99UGA03349, 99UGA07412, or 98UG57128. 
     
     
         2 . The pharmaceutical composition of  claim 1  comprising 99UGA03349 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         3 . The pharmaceutical composition of  claim 1  comprising 99UGA07412 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         4 . The pharmaceutical composition of  claim 1  comprising 99UGA03349 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         5 . The pharmaceutical composition of  claim 1  comprising 99UGA07412 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         6 . The pharmaceutical composition of  claim 1  comprising 98UG57128 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said recombinant MVA virus is MVA/UGD-1 defined as comprising 99UGA07412 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 99UGA07412 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein said recombinant MVA virus is MVA/UGD-2 defined as comprising 99UGA03349 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 98UG57128 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein said recombinant MVA virus is MVA/UGD-3 defined as comprising 99UGA07412 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 99UGA03349 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein said recombinant MVA virus is MVA/UGD-4 defined as comprising 99UGA03349 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 99UGA07412 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein said recombinant MVA virus is MVA/UGD-5 defined as comprising 99UGA03349 gagpol in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 98UG57128 envelope in Appendix 1 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         12 . The pharmaceutical composition of  claim 1  wherein said recombinant MVA virus additionally expresses an additional HIV gene or modified gene thereof for production of an HIV antigen by expression from said recombinant MVA virus, wherein said additional HIV gene is a member selected from the group consisting of vif, vpr, tat, rev, vpu, and nef. 
     
     
         13 . An MVA shuttle plasmid comprising pLAS-1 of Appendix 2 or sequence having at least about 90%, 95% or 99.9% identity thereto, or pLAS-2 of Appendix 2 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         14 . A method of making a recombinant MVA virus comprising preparing the MVA shuttle plasmid of  claim 13  and combining said MVA shuttle plasmid with a MVA virus to produce said recombinant MVA virus, and isolating said recombinant MVA virus. 
     
     
         15 . A method of boosting a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 1 , whereby a CD8 +  T cell immune response to the antigen previously primed in the primate is boosted. 
     
     
         16 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 1 , whereby a CD8 +  T cell immune response to the antigen in the primate is induced. 
     
     
         17 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a priming composition comprising nucleic acid encoding said antigen and then provision in the primate of a boosting composition which comprises  claim 1 , whereby a CD8 +  T cell immune response to the antigen is induced. 
     
     
         18 . The method of  claim 15 , wherein the primate is a human. 
     
     
         19 . The method of  claim 15 , wherein administration of the recombinant MVA virus is by needleless injection. 
     
     
         20 . The method of  claim 15 , wherein the priming composition comprises plasmid DNA encoding said antigen. 
     
     
         21 . MVA 1974/NIH Clone 1. 
     
     
         22 . A pharmaceutical composition comprising a recombinant MVA virus expressing an HIV env, gag, and pol gene or modified gene thereof for production of an HIV Env, Gag, and Pol antigen by expression from said recombinant MVA virus, wherein said HIV env gene is modified to encode an HIV Env protein composed of gp120 and the membrane-spanning and ectodomain of gp41 but lacking part or all of the cytoplasmic domain of gp41, and a pharmaceutically acceptable carrier, wherein said HIV env, gag, and pol genes are isolatable from an individual infected with Kenyan clade A isolate 00KE-KER2008, 00KE-KNH1144, or 00KE-KNH1207. 
     
     
         23 . The pharmaceutical composition of  claim 22  comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         24 . The pharmaceutical composition of  claim 22  comprising 00KE-KNH1144 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         25 . The pharmaceutical composition of  claim 22  comprising 00KE-KNH1207 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         26 . The pharmaceutical composition of  claim 22 , wherein said recombinant MVA virus is MVA/KEA-1 defined as comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00KE-KNH1144 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         27 . The pharmaceutical composition of  claim 22 , wherein said recombinant MVA virus is MVA/KEA-2 defined as comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00KE-KNH1207 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         28 . The pharmaceutical composition of  claim 22 , wherein said recombinant MVA virus is MVA/KEA-3 defined as comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00KE-KNH1144 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         29 . The pharmaceutical composition of  claim 22 , wherein said recombinant MVA virus is MVA/KEA-4 defined as comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00KE-KNH1144 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         30 . The pharmaceutical composition of  claim 22 , wherein said recombinant MVA virus is MVA/KEA-5 defined as comprising 00KE-KNH2008 gagpol in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00KE-KNH1144 envelope in Appendix 3 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         31 . The pharmaceutical composition of  claim 22  wherein said recombinant MVA virus additionally expresses an additional HIV gene or modified gene thereof for production of an HIV antigen by expression from said recombinant MVA virus, wherein said additional HIV gene is a member selected from the group consisting of vif, vpr, tat, rev, vpu, and nef. 
     
     
         32 . A method of boosting a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 22 , whereby a CD8 +  T cell immune response to the antigen previously primed in the primate i2s boosted. 
     
     
         33 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 22 , whereby a CD8 +  T cell immune response to the antigen in the primate is induced. 
     
     
         34 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a priming composition comprising nucleic acid encoding said antigen and then provision in the primate of a boosting composition which comprises  claim 22 , whereby a CD8 +  T cell immune response to the antigen is induced. 
     
     
         35 . The method of  claim 32 , wherein the primate is a human. 
     
     
         36 . The method of  claim 32 , wherein administration of the recombinant MVA virus is by needleless injection. 
     
     
         37 . The method of  claim 32 , wherein the priming composition comprises plasmid DNA encoding said antigen. 
     
     
         38 . A pharmaceutical composition comprising a recombinant MVA virus expressing an HIV env, gag, and pol gene or modified gene thereof for production of an HIV Env, Gag, and Pol antigen by expression from said recombinant MVA virus, wherein said HIV env gene is modified to encode an HIV Env protein composed of gp120 and the membrane-spanning and ectodomain of gp41 but lacking part or all of the cytoplasmic domain of gp41, and a pharmaceutically acceptable carrier, wherein said HIV env, gag, and pol genes are isolatable from an individual infected with Tanzanian clade C isolate 00TZA-246 or 00TZA-125. 
     
     
         39 . The pharmaceutical composition of  claim 38  comprising 00TZA-246 gagpol in Appendix 4 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         40 . The pharmaceutical composition of  claim 38  comprising 00TZA-125 envelope in Appendix 4 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         41 . The pharmaceutical composition of  claim 38 , wherein said recombinant MVA virus is MVA/TZC-1 defined as comprising 00TZA-246 gagpol in Appendix 4 or sequence having at least about 90%, 95% or 99.9% identity thereto, and 00TZA-125 envelope in Appendix 4 or sequence having at least about 90%, 95% or 99.9% identity thereto. 
     
     
         42 . The pharmaceutical composition of  claim 38  wherein said recombinant MVA virus additionally expresses an additional HIV gene or modified gene thereof for production of an HIV antigen by expression from said recombinant MVA virus, wherein said additional HIV gene is a member selected from the group consisting of vif, vpr, tat, rev, vpu, and nef. 
     
     
         43 . A method of boosting a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 38 , whereby a CD8 +  T cell immune response to the antigen previously primed in the primate is boosted. 
     
     
         44 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a composition of  claim 38 , whereby a CD8 +  T cell immune response to the antigen in the primate is induced. 
     
     
         45 . A method of inducing a CD8 +  T cell immune response to an HIV Env, Gag, or Pol antigen in a primate, the method comprising provision in the primate of a priming composition comprising nucleic acid encoding said antigen and then provision in the primate of a boosting composition which comprises  claim 38 , whereby a CD8 +  T cell immune response to the antigen is induced. 
     
     
         46 . The method of  claim 43 , wherein the primate is a human. 
     
     
         47 . The method of  claim 43 , wherein administration of the recombinant MVA virus is by needleless injection. 
     
     
         48 . The method of  claim 43 , wherein the priming composition comprises plasmid DNA encoding said antigen.