Synergistic Attenuation of Vesicular Stomatitis Virus, Vectors Thereof and Immunogenic Compositions Thereof
AssigneeWyeth
InventorsDavid Kirkwood Clarke, Roger Michael Hendry, Stephen A. Udem, Christopher Lee Parks
Life of this patent
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Abstract
The present invention broadly relates to the synergistic attenuation of vesicular stomatitis virus (VSV), More particularly, the invention relates to the identification of combined mutation classes which synergistically attenuate the pathogenicity of VSV vectors in mammals and immunogenic compositions thereof.
Claims37
A genetically modified vesicular stomatitis virus (VSV) comprising at least two different classes of mutations in its genome, the mutations selected from the group consisting of a temperature-sensitive (ts) mutation, a point mutation, a gene shuffling mutation, A G-stem mutation, a non-cytopathic M gene mutation, an ambisense RNA mutation, a truncated G gene mutation, a G gene insertion mutation and a gene deletion mutation, wherein the two mutations synergistically attenuate VSV pathogenicity.
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A method of immunizing a mammalian host against bacterial infection comprising, administering an immunogenic dose of a genetically modified VSV vector comprising:
- (a) at least two different classes of mutations in its genome, the mutations selected from the group consisting of a ts mutation, a point mutation, a gene shuffling mutation, a G-stem mutation, a non-cyto-pathic M gene mutation, an ambisense RNA mutation, a truncated G gene mutation, a G gene insertion mutation and a gene deletion mutation, wherein the two mutations synergistically attenuate VSV pathogenicity;
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- (b) at least one foreign RNA sequence inserted into orreplacing a region of the VSV genome non-essential for replication, wherein the RNA encodes a bacterial protein selected from the group consisting of Vibrio cholerae protein, a Streptococcus pneumoniae protein, Streptococcus pyogenes protein, a Streptococcus agalactiae protein, a Helicobacter pylori protein, a Neisseria meningitidis protein, a Neisseria gonorrheae protein, a Corynebacteria diphtheriae protein, a Clostridium tetani protein, a Bordetella pertussis protein, a Haemophilus protein, a Chlamydia protein and a Escherichia coli protein.
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A method of immunizing a mammalian host against viral infection comprising administering an immunogenic dose of a genetically modified VSV vector comprising:
- (a) at least two different classes of mutations in its genome, the mutations selected from the group consisting of a ts mutation, a point mutation, a gene shuffling mutation, a G-stem mutation, a non-cyto-pathic M gene mutation, an ambisense RNA mutation, a truncated G gene mutation, a G gene insertion mutation a gene deletion mutation, wherein the two mutations synergistically attenuate VSV pathogenicity;
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- (b) at least one foreign RNA sequence inserted into or replacing a region of the VSV genome non-essential for replication, wherein the RNA encodes a viral protein selected from the group consisting of a HIV protein, a HTLV protein, a SIV protein, A RSV protein, a PIV protein, a HSV protein, a CMV protein, an Epstein-Barr virus protein, a Varicella-Zoster virus protein, a mumps virus protein, a measles virus protein, an influenza virus protein, a poliovirus protein, a rhinovirus protein, a hepatitis A virus protein, a hepatitis B virus protein, a hepatitis C virus protein, a Norwalk virus protein, a togavirus protein, an alphavirus protein, a rubella virus protein, a rabies virus protein, a Marburg virus protein, an Ebola virus protein, a papilloma virus protein, a polyoma virus protein, a metapneumovirus protein and a coronavirus protein.
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Dependencies are inferred from the claim text.