US2013323278A1PendingUtilityA1

Chimeric Flavivirus Vaccines

67
Individually held — no corporate assignee on recordPriority: Feb 28, 1997Filed: Dec 3, 2012Published: Dec 5, 2013
Est. expiryFeb 28, 2017(expired)· nominal 20-yr term from priority
Inventors:Thomas J. Chambers
A61K 39/29C12N 7/00C12N 2770/24134C07K 2319/02C12N 2770/24161A61K 39/193A61P 35/00C12N 2770/24143C12N 2770/24162A61K 39/12A61P 31/14C12N 2770/24122A61K 35/13C07K 14/005A61K 2039/5256A61K 2039/5254A61K 48/00A61K 39/00Y02A50/30
67
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Claims

Abstract

A chimeric live, infectious, attenuated virus containing a yellow fever virus, in which the nucleotide sequence for a prM-E protein is either deleted, truncated, or mutated, so that functional prM-E protein is not expressed, and integrated into the genome of the yellow fever virus, a nucleotide sequence encoding a prM-E protein of a second, different flavivirus, so that the prM-E protein of the second flavivirus is expressed.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A chimeric live, infectious, attenuated virus, comprising:
 a yellow fever virus in which the nucleotide sequence encoding a prM-E protein is either deleted, truncated, or mutated so that functional yellow fever virus prM-E protein is not expressed, and   integrated into the genome of said yellow fever virus, a nucleotide sequence encoding a prM-E protein of a second, different flavivirus, so that said prM-E protein of said second flavivirus is expressed.   
     
     
         2 . The chimeric virus of  claim 1 , wherein said second flavivirus is a Japanese Encephalitis (JE) virus. 
     
     
         3 . The chimeric virus of  claim 1 , wherein said second flavivirus is a Dengue virus selected from the group consisting of Dengue types 1, 2, 3, and 4. 
     
     
         4 . The chimeric virus of  claim 3 , wherein said nucleotide sequences derived from said Dengue virus are derived from two or more different Dengue strains. 
     
     
         5 . The chimeric virus of  claim 1 , wherein said second flavivirus is selected from the group consisting of a Murray Valley Encephalitis virus, a St. Louis Encephalitis virus, a West Nile virus, a Tick-borne Encephalitis virus (i.e., a Central European Encephalitis virus or a Russian Spring-Summer Encephalitis virus), a Hepatitis C virus, a Kunjin virus, a Powassan virus, a Kyasanur Forest Disease virus, and an Omsk Hemorrhagic Fever virus. 
     
     
         6 . The chimeric virus of  claim 1 , wherein the nucleotide sequence encoding the prM-E protein of said second, different flavivirus replaces the nucleotide sequence encoding the prM-E protein of said yellow fever virus. 
     
     
         7 . The chimeric virus of  claim 1 , wherein said nucleotide sequence encoding said prM-E protein of said second, different flavivirus comprises a mutation that prevents prM cleavage to produce M protein. 
     
     
         8 . The chimeric virus of  claim 1 , wherein the prM signal of said chimeric virus is that of yellow fever virus. 
     
     
         9 . The chimeric virus of  claim 1 , wherein the NS2B-NS3 protease recognition site and the signal sequences and cleavage sites at the C/prM and E/NS1 junctions are maintained in construction of said chimeric flavivirus. 
     
     
         10 . A method of preventing or treating flavivirus infection in a patient, said method comprising administering to said patient a chimeric, live, infectious, attenuated virus comprising:
 a yellow fever virus in which the nucleotide sequence encoding a prM-E protein is either deleted, truncated, or mutated so that functional yellow fever virus prM-E protein is not expressed, and   integrated into the genome of said yellow fever virus, a nucleotide sequence encoding a prM-E protein of a second, different flavivirus, so that said prM-E protein of said second flavivirus is expressed.   
     
     
         11 . The method of  claim 10 , wherein said second flavivirus is a Japanese Encephalitis (JE) virus. 
     
     
         12 . The method of  claim 10 , wherein said second flavivirus is a Dengue virus selected from the group consisting of Dengue types 1, 2, 3, and 4. 
     
     
         13 . The method of  claim 12 , wherein said nucleotide sequences derived from said Dengue virus are derived from two or more different Dengue strains. 
     
     
         14 . The method of  claim 10 , wherein said second flavivirus is selected from the group consisting of a Murray Valley Encephalitis virus, a St. Louis Encephalitis virus, a West Nile virus, a Tick-borne Encephalitis virus, a Hepatitis C virus, a Kunjin virus, a Central European Encephalitis virus, a Russian Spring-Summer Encephalitis virus, a Powassan virus, a Kyasanur Forest Disease virus, and an Omsk Hemorrhagic Fever virus. 
     
     
         15 . The method of  claim 10 , wherein the nucleotide sequence encoding the prM-E protein of said second, different flavivirus replaces the nucleotide sequence encoding the prM-E protein of said yellow fever virus. 
     
     
         16 . The method of  claim 10 , wherein said nucleotide sequence encoding said prM-E protein of said second, different flavivirus comprises a mutation that prevents prM cleavage to produce M protein. 
     
     
         17 . The method of  claim 10 , wherein the prM signal of said chimeric virus is that of yellow fever virus. 
     
     
         18 . The method of  claim 10 , wherein the NS2B-NS3 protease recognition site and the signal sequences and cleavage sites at the C/prM and E/NS1 junctions are maintained in construction of said chimeric flavivirus. 
     
     
         19 . A nucleic acid molecule encoding a chimeric live, infectious, attenuated virus comprising:
 a yellow fever virus in which the nucleotide sequence encoding a prM-E protein is either deleted, truncated, or mutated so that functional yellow fever virus prM-E protein is not expressed, and   integrated into the genome of said yellow fever virus, a nucleotide sequence encoding a prM-E protein of a second, different flavivirus, so that said prM-E protein of said second flavivirus is expressed.   
     
     
         20 . The nucleic acid molecule of  claim 19 , wherein said second flavivirus is a Japanese Encephalitis (JE) virus. 
     
     
         21 - 32 . (canceled)

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