US2003223987A1PendingUtilityA1

Immunodeficiency recombinant poxvirus

61
Priority: Mar 7, 1991Filed: May 20, 2003Published: Dec 4, 2003
Est. expiryMar 7, 2011(expired)· nominal 20-yr term from priority
Inventors:Enzo PaolettiJames TartagliaWilliam I. CoxRobert C. GalloGenoveffa Franchini
C12N 2760/20122C12N 2710/24143C12N 2760/20022C12N 2740/16122C12N 2710/24022C12N 2740/13022A61P 31/12C12N 2760/12022A61P 31/18C07K 2319/00C12N 2770/24022A61P 37/04C12N 2760/18722C12N 2710/24043C12N 15/86C12N 2770/24143C12N 2710/16222C12N 2710/24122C12N 2740/16222C12N 2770/24122C07K 14/005C12N 2760/18122A61P 37/02C12N 2710/16722C12N 2750/14322C12N 2740/16322C12N 2710/16622C12N 2730/10122C12N 2760/16122C12N 2740/15022A61K 2039/5254C07K 14/33A61K 39/00
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Claims

Abstract

Attenuated recombinant viruses containing DNA encoding an immunodeficiency virus and/or CTL antigen, as well as methods and compositions employing the viruses, expression products therefrom, and antibodies generated from the viruses or expression products, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least one of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, ELDKWA or LDKW epitopes, preferably HIV1gag(+pro)(IIIB), gp120(MN) (+transmembrane), two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL epitopes; or two ELDKWA in gp120 V3 or another region or in gp160. The two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL epitopes are preferably CTL1, CTL2, pol1, pol2 and pol3. The recombinant viruses and gene products therefrom and antibodies generated by the viruses and gene products have several preventive, therapeutic and diagnostic uses. DNA from the recombinant viruses are useful as probes or, for generating PCR primers or for immunization. Also disclosed and claimed are HIV immunogens and modified gp160 and gp120.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A modified recombinant virus, said modified recombinant virus having virus-encoded genetic functions inactivated therein so that the virus has attenuated virulence, yet retained efficacy; said virus further comprising exogenous DNA in a nonessential region of the virus genome, said exogenous DNA encoding at least one immunodeficiency virus epitope.  
     
     
         2 . The virus of  claim 1  wherein said virus is a poxvirus.  
     
     
         3 . The virus of  claim 2  wherein the poxvirus is a vaccinia virus.  
     
     
         4 . The virus of  claim 3  wherein the genetic functions are inactivated by deleting at least one open reading frame.  
     
     
         5 . The virus of  claim 4  wherein the deleted genetic functions include a C7L−K1L open reading frame, or, a host range region.  
     
     
         6 . The virus of  claim 5  wherein at least one additional open reading frame is deleted; and, the additional open reading frame is selected from the group consisting of: J2R, B13R+B14R, A26L, A56R, and I4L.  
     
     
         7 . The virus of  claim 5  wherein at least one additional open reading frame is deleted; and, the additional open reading frame is selected from the group consisting of: a thymidine kinase gene, a hemorrhagic region, an A type inclusion body region, a hemagglutinin gene, and a large subunit, ribonucleotide reductase.  
     
     
         8 . The virus of  claim 6  wherein J2R, B13R+B14R, A26L, A56R, C7L−K1L and I4L are deleted from the virus.  
     
     
         9 . The virus of  claim 7  wherein a thymidine kinase gene, a hemorrhagic region, an A type inclusion body region, a hemagglutinin gene, a host range region, and a large subunit, ribonucleotide reductase are deleted from the virus.  
     
     
         10 . The virus of  claim 8  which is a NYVAC recombinant virus.  
     
     
         11 . The virus of  claim 9  which is a NYVAC recombinant virus.  
     
     
         12 . The virus of  claim 11  wherein the exogenous DNA codes for at least one of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, and ELDKWA or LDKW epitopes.  
     
     
         13 . The virus of  claim 12  wherein the exogenous DNA codes for HIV1gag (+pro)(IIIB), gp120(MN)(+transmembrane), two nef(BRU)CTL and three pol(IIIB)CTL epitopes; or, two ELDKWA epitopes.  
     
     
         14 . The virus of  claim 13  wherein the two nef(BRU)CTL and three pol(IIIB)CTL epitopes are: CTL1, CTL2, pol1, pol2 and pol3.  
     
     
         15 . The virus of  claim 12  wherein the ELDKWA or LDKW epitopes are expressed as part of a region of gp120 or a region of gp160.  
     
     
         16 . The virus of  claim 15  wherein the ELDKWA or LDKWA epitopes are expressed as part of gp120 V3.  
     
     
         17 . A modified recombinant avipox virus which is modified so that it has attenuated virulence in a host; and, which contains exogenous DNA in a nonessential region of the virus genome, said exogenous DNA encoding at least one immunodeficiency virus epitope.  
     
     
         18 . The virus of  claim 17  wherein said virus is a canarypox virus.  
     
     
         19 . The virus of  claim 18  wherein the canarypox virus is a Rentschler vaccine strain which was attenuated through more than 200 serial passages on chick embryo fibroblasts, a master seed therefrom was subjected to four successive plaque purifications under agar, from which a plaque clone was amplified through five additional passages.  
     
     
         20 . The virus of  claim 18  which is an ALVAC recombinant virus.  
     
     
         21 . The virus of  claim 18  wherein the exogenous DNA codes for at least one of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, and ELDKWA or LDKW epitopes.  
     
     
         22 . The virus of  claim 18  wherein the exogenous DNA codes for at least one of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), two nef(BRU)CTL and three pol(IIIB)CTL epitopes; or two ELKDWA epitopes.  
     
     
         23 . The virus of  claim 21  wherein the ELDKWA or LDKWA epitopes are expressed as part of a region of gp120 or a region of gp160.  
     
     
         24 . The virus of  claim 23  wherein the ELDKWA or LDKWA epitopes are expressed as part of gp120 V3.  
     
     
         25 . The virus of  claim 22  wherein the two nef(BRU)CTL and three pol(IIIB)CTL epitopes are: CTL1, CTL2, pol1, pol2 and pol3.  
     
     
         26 . The virus of  claim 21  which is vCP205 (ALVAC-MN120TMG), vCP264 (ALVAC-MN120TMGN), vCP300 (ALVAC-MN120TMGNP), or vCP1307.  
     
     
         27 . vP1313 or vP1319.  
     
     
         28 . A method for treating a patient in need of immunological treatment or of inducing an immunological response in an individual comprising administering to said patient or individual a composition comprising a virus as claimed in any one of claims  1 ,  12 ,  14 ,  21 ,  26  or  27  in admixture with a suitable carrier.  
     
     
         28 . A composition for inducing an immunological response comprising a virus as claimed in any one of claims  1 ,  12 ,  14 ,  21 ,  26  or  27  in admixture with a suitable carrier.  
     
     
         29 . A method for expressing a gene product in a cell cultured in vitro comprising introducing into the cell a virus as claimed in any one of claims  1 ,  12 ,  14 ,  21 ,  26  or  27 .  
     
     
         29 . An immunodeficiency virus antigen prepared from in vitro expression of a virus as claimed in any one of claims  1 ,  12 ,  14 ,  19 ,  22  or  23 .  
     
     
         30 . An antibody elicited by in vivo expression of an antigen from a virus as claimed in any one of claims  1 ,  12 ,  14 ,  19 ,  22  or  23  or, by administration of an immunodeficiency virus associated antigen from in vitro expression of the virus.  
     
     
         31 . An HIV immunogen selected from the group consisting of: HIV1gag(+pro)(IIIB), gp120(MN)(+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, and ELDKWA or LDKW epitopes.  
     
     
         32 . The HIV immunogen of  claim 31  wherein the ELDKWA or LDKWA is part of a region of gp120 or a region of gp160.  
     
     
         33 . The HIV immunogen of  claim 32  wherein the ELDKWA or LDKWA is part of gp120 V3.  
     
     
         34 . A gp120 or gp160 modified so as to contain an epitope not naturally occurring in gp120 or gp160.  
     
     
         35 . The gp120 or gp160 of  claim 34  modified so as to contain a B-cell epitope not naturally occurring in gp120 or gp160.  
     
     
         36 . The gp120 or gp160 or  claim 34  which is a gp120 modified in the V3 loop so as to contain an epitope not naturally occurring on the gp120 V3 loop.  
     
     
         37 . The gp160 or gp120 of  claim 36  wherein teh epitope is a B-cell epitope.  
     
     
         38 . The gp160 or gp120 or  claim 36  wherein the eiptope is ELDKWA or LDKWA.  
     
     
         39 . The gp160 or gp120 of  claim 34  which is a gp120 modified to contain at least one of HIV1gag(+pro)(IIIB), gp120(MN) (+transmembrane), nef(BRU)CTL, pol(IIIB)CTL, and ELDKWA or LDKW epitopes.  
     
     
         40 . The gp160 of gp120 of  claim 39  wherein the gp120 is modified in the V3 loop to contain the epitope.

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