TH75852A - Weakening of the synergistic effect of viral stomatitis. Its vectors and their immune mixtures - Google Patents

Abstract

DC60 This invention involves a broad With a weak, adjuvant activity of vesicular viral stomatitis (VSV), especially This invention involves the identification of the type of aggregation that does Provides synergistic effect on the pathogenesis of weaker mammalian VSV vectors and mixtures. Build up their immunity This invention involves a broad With a weak, adjuvant activity of vesicular viral stomatitis (VSV), especially This invention involves the identification of the type of aggregation that does Provides synergistic effect on the pathogenesis of weaker mammalian VSV vectors and mixtures. Build up their immunity

Claims (144)

1. Genetically modified vesicular stomatitis virus (VSV) containing at least two different types of mutations in its genome. The mutations are selected from a group comprising temperature-sensitive mutations (ts), site mutations, transposition mutations, G-stem mutations, non-cytopathic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G insertion mutations, and deletion mutations, where two mutations result in synergistic pathogenicity. 2. The VSV of claim 1, where the pre-disease capacity is further defined as the capacity to induce neuropathy. 3. VSV of claim 1, where the second mutation is a truncated mutation of gene N, which is swapped with another gene. 4. VSV of claim 3 where the G protein encoded by the truncated G gene has a deletion of twenty post-carboxylic acid amino acids. 5. VSV of claim 3 where the G protein encoded by the truncated G gene has a deletion of twenty-eight post-carboxylic acid amino acids. 6. VSV of claim 3 where the G protein encoded by the cleavaged G gene has a cytoplasmic tail domain containing a single amino acid. 7. VSV of claim 3 where the G protein encoded by the truncated G gene has a cytoplasmic tail domain composed of nine amino acids. 8. VSV of claim 3 where gene N is swapped to 3'-PNMGL-5' or 3'-PMNGL-5' associated with the wild-type 3'-NPMGL-5' genome VSV, where N is the gene encoded in nucleocapsid protein, P is the gene encoded in phosphoprotein, M is the gene encoded in matrix protein, G is the gene encoded in attachment glycosidic protein, and L is the gene encoded in RNA-dependent polymerase protein. 9. The VSV of claim 3 consists of a selected mutant genome from a pool comprising 3'-PNMG(ct-1)L-5', 3'-PMNG(ct-9)L-5', 3'-NPMG(ct-1)L-5', and 3'-PMNG(ct-9)L-5', where N is the gene encoding nucleocapsid protein, P is the gene encoding phosphoprotein, M is the gene encoding matrix protein, G(ct-1) is the gene encoding attachment glycoprotein with twenty-post-carboxylic acid deletions, G(ct-9) is the gene encoding attachment glycoprotein with twenty-post-carboxylic acid deletions, and L is the gene encoding RNA-dependent polymerase protein. 10. VSV of claim 9, where the mutant genome is 3'-PMNG(ct-9)L-5'. 11. VSV of claim 9, where the mutant genome is 3'-PMNG(ct-1)L-5'. 12. The VSV of claim 9, which is further comprised of a third type of mutation in its genome, where the mutation is a ts mutation, an ambisense RNA mutation, a non-cytopathic M gene mutation, a gene deletion, a G gene insertion, or a site mutation. 13. VSV of claim 1 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has a LD50 100 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 14. VSV of claim 1 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has an LD50 1,000 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 15. VSV of claim 1 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has an LD50 1,000 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 16. VSV of claim 1 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has an LD50 100,000 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 17. VSV of claim 1, where the second mutation is a truncated G gene mutation and a non-cytopathic M gene mutation. 18. VSV of claim 17 where the G protein encoded by the truncated G gene has a deletion of twenty post-carboxylic acid amino acids. 19. VSV of claim 17 where the G protein encoded by the truncated G gene has a deletion of twenty-eight post-carboxylic acid amino acids. 20. VSV of claim 17 where the G protein encoded by the truncated G gene has a cytoplasmic tail domain composed of one of nine amino acid sets. 21. VSV of claim 17 where the G protein encoded by the cleavaged G gene has a cytoplasmic tail domain composed of nine amino acids. 22. VSV of claim 17, where the non-cytopathic mutation of gene M (M(ncp) is the mutation of methionine 33 and methionine 51 of gene M. 23. VSV of claim 17, which includes a mutant genome of 3'-NP M(ncp)G(ct-1)L-5' or 3'-NP M(ncp)G(ct-9)L-5'. 24. The VSV of claim 17 is further comprised of a third type of mutation in its genome, where the mutation is a ts mutation, ambisense RNA mutation, transposition mutation, deletion mutation, insertion mutation, G insertion mutation, G-stem mutation, or site mutation. 25. VSV of claim 1 where the two mutations are the ts N mutation (N(ts)) and the ts L mutation (L(ts)). 26. VSV of claim 25, which contains the mutant genome of 3'N(ts)PMGL(ts)-5'. 27. The VSV of claim 25, which is further comprised of a third type of mutation in its genome, where the mutation is a site mutation, a gene swap 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. 28. VSV of Claim 1, where one type of mutation is the G-stem mutation. 29. A genetically modified VSV vector containing at least two different types of mutations in its genome. The mutations are selected from a group comprising ts mutations, spot mutations, gene swapping mutations, G-stem mutations, non-cytopathic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G gene insertion mutations, and gene deletion mutations, and at least one foreign RNA sequence inserted into or replacing a region of the VSV genome not required for replication, where two mutations result in synergistic attenuation of the VSV's pathogenicity. 30. The vector of claim 29, where pathogenicity is further defined as the ability to cause neuropathic disease. 31. Vector of claim 29, where foreign RNA is defined as an open read frame (ORF). 32. Vector of claim 29 where the two mutations are a cut gene G mutation and a gene N swap mutation. 33. Vector of claim 32 where the G protein encoded by the truncated G gene has twenty deletions of the last carboxylic amino acids. 34. Vector of claim 32 where the G protein encoded by the truncated G gene has a deletion of twenty-eight post-carboxylic acid amino acids. 35. A vector of claim 32 where protein G encoded by the cleavaged G gene has a cytoplasmic tail domain consisting of a single set of amino acids. 36. A vector of claim 32 where the G protein encoded by the cleavaged G gene has a cytoplasmic tail domain composed of nine amino acids. 37. Vector of claim 32 where gene N is swapped to 3'-PNMGL-5' or 3'-PMNGL-5' associated with the 3'-NPMGL-5' wild-type VSV genome, where N is the gene encoded in nucleocapsid protein, P is the gene encoded in phosphoprotein, M is the gene encoded in matrix protein, G is the gene encoded in attachment glycoprotein, and L is the gene encoded in RNA-dependent polymerase protein. 38. A vector of claim 32 consisting of a selected mutant genome from a group comprising 3'-PNMG(c1-1)L-5', 3'-PNMG(ct-9)L-5', 3'-PMNG(ct-1)L-5', and 3'-PMNG(ct-9)L-5', where N is the gene encoding nucleocapsid protein, P is the gene encoding phosphoprotein, M is the gene encoding matrix protein, G(ct-1) is the gene encoding attachment glycoprotein with twenty-eight post-carboxy amino acid deletions, G(ct-9) is the gene encoding attachment glycoprotein with twenty post-carboxy amino acid deletions, and L is the gene encoding RNA-dependent polymerase protein. 39. Vector of claim 38, where the mutant genome is 3'-PMNG(ct-1)L-5'. 40. Vector of claim 38, where the mutant genome is 3'-PMNG(ct-1)L-5'. 41. A vector of claim 38, which is further comprised of a third type of mutation in its genome, where the mutation is a ts mutation, a site mutation, an ambisense RNA mutation, a deletion mutation, a gene insertion mutation, or a non-cytopathic M gene mutation. 42. Vector of claim 32 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has a LD50 100 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 43. Vector of claim 32 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has an LD50 1,000 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 44. Vector of claim 32 where VSV injected intracranially into 4-week-old Swiss-Webster female mice has an LD50 10,000 times greater than that of wild-type VSV injected intracranially into 4-week-old Swiss-Webster female mice. 45. The vector of claim 32, where VSV injected in the skull into 4-week-old Swiss-Webster female mice has an LD50 100,000 times greater than that of wild-type VSV injected in the skull into 4-week-old Swiss-Webster female mice. 46. Vector of claim 32 where foreign RNA is selected from a group comprising the following genes: HIV, HTLV, SIV, RSV, PIV, HSV, CMV, Epstein-Barr virus, varicella-zoster virus, mumps virus, measles virus, influenza virus, poliovirus, rhinovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, Norwalk virus, togavirus, alphavirus, rubella virus, rabies virus, Marburg virus, Ebola virus, papillomavirus, polyoma virus, metapneumovirus, coronavirus, vibriozolera, etc. Streptococcus pneumoniae gene, Streptococcus pyogenes gene, Helidobacter pylori gene, Streptococcus agalactia gene, Nisseria meningitidis gene, Nisseria gonorrhoea gene, Corine bacterial diphtheria gene, Clostridium tetanus gene, Bordetella pertussis gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, psychokineses encoded genes, auxiliary T epitopes encoded genes, CTL epitopes encoded genes, complementary encoded genes, and cofactor encoded genes. 47. A vector of claim 46 where the HIV gene is selected from a group consisting of gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 48. The vector of claim 47, where the HIV gene is gag. 49. The vector of claim 48, where the mutant genome is 3'-gag1-PNMG(ct-1)L-5', 3'-gag1-PNMG(ct-9)L-5', 3'-gag1-PMNG(ct-1)L-5', 3'-gag1-PMNG(ct-9)L-5', 3'-pNMG(ct-1)L-gag5-5',3'-PNMG(ct-9)L-gag5-5',3'-PMNG(ct-1)L-gag5-5', or 3'-PMNG(ct-9)L-gag5-5'. 50. Vector of claim 29 where the two mutations are a truncated G gene mutation and a non-cytopathic M gene mutation. 51. Vector of claim 50 where the G protein encoded by the cleavaged G gene has a deletion of twenty-eight post-carboxylic acid amino acids. 52. Vector of claim 50 where the G protein encoded by the cleavaged G gene has a cytoplasmic tail domain consisting of one amino acid. 53. Vector of claim 50, where the non-cytopathic mutation of gene M (M(ncp)) is the methionine 33 and methionine 51 mutation of gene M. 54. A vector of claim 50 containing a mutant genome of 3'-NPM(ncp)G(ct-1)L-5' or 3'-NPM(ncp)G(ct-9)L-5'. 55. A vector of claim 50, which is further comprised of three types of mutations in its genome, where the mutations are ts mutations, site mutations, transposition mutations, G-stem mutations, ambisense RNA mutations, G insertion mutations, and deletion mutations. 56. Vector of claim 50 where foreign RNA is selected from a group comprising the following genes: HIV gene, HTLV gene, SIV gene, RSV gene, PIV gene, HSV gene, CMV gene, Epstein-Barr virus gene, Varicella-Zoster virus gene, Mumps virus gene, Measles virus gene, Influenza virus gene, Poliovirus gene, Rhinovirus gene, Hepatitis A virus gene, Hepatitis B virus gene, Hepatitis C virus gene, Norwalk virus gene, Tokavirus gene, Alphavirus gene, Rubella virus gene, Rabies virus gene, Marburg virus gene, Ebola virus gene, Papillomavirus gene, Polyoma virus gene, Metapneumovirus gene, Coronavirus gene, Vibrio solera gene, etc. Streptococcus pneumoniae gene, Streptococcus piogenase gene, Helicobacter piori gene, Streptococcus agalactia gene, Nisseria meningitidis gene, Nisseria gonorrhoea gene, Corine bacterium dipteris gene, Clostridium tetanus gene, Bordetella pertussis gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, Psychodine encoding gene, T epitope encoding gene, CTL epitope encoding gene, complementary encoding gene, and cofactor encoding gene. 57. A vector of claim 56 where the HIV gene is selected from a group consisting of gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 58. The vector of claim 56, where the HIV gene is: 59. Vector of claim 58, where the mutant genome is 3'-gag1-NPM(ncp)G(ct-1)L-5', 3'-gag1-NPM(ncp)G(ct-9)L-5', 3'-NPM(ncp)G(ct-1)gag5-5', or 3'-NPM(ncp)G(ct-9)gag5-5'. 60. Vector of claim 29 where the two mutations are the mutation of the gene ts N (N(ts)) and the mutation of the gene ts L (L(ts)). 61. Vector of claim 60 containing a mutant genome of 3'-N(ts)PMGL(ts)-5'. 62. The vector of claim 60, which is further comprised of a third type of mutation in its genome, where mutations are site mutations, gene swap mutations, G-stem mutations, non-cytopathic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G gene insertion mutations, and gene deletion mutations. 63. Vector of claim 60 where foreign RNA is selected from a group comprising the following genes: HIV, HTLV, SIV, RSV, PIV, HSV, CMV, Epstein-Barr virus, Varicella-Zoster virus, Mumps virus, Measles virus, Influenza virus, Poliovirus, Rhinovirus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Norwalk virus, Tokavirus, Alphavirus, Rubella virus, Rabies virus, Marburg virus, Ebola virus, Papillomavirus, Polyoma virus, Metapneumovirus, Coronavirus, Vibrio solera, etc. Streptococcus pneumoniae gene, Streptococcus piogenase gene, Helitobacter piori gene, Streptococcus agalactia gene, Nisseria meningitidis gene, Nisseria gonorrhoea gene, Corine gene, Bacterial dipteris gene, Clostridium tetanis gene, Bordetella pertussis gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, cytokine encoding gene, T epitope encoding gene, CTL epitope encoding gene, complementary encoding gene, and cofactor encoding gene. 64. Vector of claim 63 where HIV validation is selected from a group comprising gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 65. The vector of claim 64, where the HIV gene is gag. 66. Vector of claim 64 where the mutant genome is 3'-gag1-N(ts)PMGL(ts)L-5' and 3'-N(ts)PMGL(ts)L-gag5-5'. 67. The vectors of claim 29, where the two mutation vectors are the G-stem mutation and the transmutation mutation. 68. The vector of claim 67, where the genome of the mutant vector is 3'-gag1-NPMG(stem)L-5'. 69. A vector of claim 68, which is further comprised of three types of mutations in its genome, where mutations are site mutations, ts mutations, gene swap mutations, non-cytopathic M gene mutations, ambisense RNA mutations, truncation G gene mutations, G gene insertion mutations, and deletion mutations. 70. Vector of claim 67 where foreign RNA is selected from a group comprising the following genes: HIV, HTLV, SIV, RSV, PIV, HSV, CMV, Epstein-Barr virus, Varicella-Zoster virus, Mumps virus, Measles virus, Influenza virus, Poliovirus, Rhinovirus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Norwalk virus, Tokavirus, Alphavirus, Rubella virus, Rabies virus, Marburg virus, Ebola virus, Papillomavirus, Polyoma virus, Metapneumovirus, Coronavirus, Vibriocholera gene, etc. Streptococcus pneumoniae gene, Streptococcus pyogenes gene, Helicobacter pylori gene, Streptococcus agalactia gene, Nisseria megitidis gene, Nisseria gonorrhoea gene, Corine bacterium, Clostridium tetanus gene, Bordetella pertussis gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, cytodine-coding gene, auxiliary epitope T-coding gene, CTL-coding gene, complementary cocoding gene, and cofactor cocoding gene. 71. An immunogenic mixture consisting of an immunogenic dose of a genetically modified VSV vector containing at least two different types of mutations in its genome. The mutations are selected from a group comprising ts mutations, spot mutations, transposition mutations, G-stem mutations, non-cytopathic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G gene insertion mutations, and gene deletion mutations, and at least one foreign RNA sequence inserted into or replacing a region of the VSV genome not necessary for transfection, where the two mutations synergistically attenuate the pathogenicity of the VSV. 72. Immunosuppressive compounds of claim 71, where pathogenicity is further defined as the ability to induce neuropathic disease. 73. Immunosynthetic mixture of claim 71, where foreign RNA is defined as the open reading frame (ORF). 74. An immunization mixture of claim 71 where the two mutations are a cut G gene mutation and an N gene swap mutation. 75. An immunogenic mixture of claim 74 where the G protein encoded by the truncated G gene has twenty deletions of the post-carboxylic acid terminus. 76. Immunosynthetic mixture of claim 74 where the G protein encoded by the truncated G gene has twenty-eight post-carboxylic acid deletions. 77. An immunogenic compound of claim 74 where the G protein encoded by the truncated G gene has a cytoplasmic tail domain consisting of a single amino acid sequence. 78. An immunization compound of claim 74 where the G protein encoded by the truncated G gene has a cytoplasmic tail domain consisting of nine amino acids. 79. Immunosynthetic mixture of claim 74 where gene N is swapped to 3'-PNMGL-5' or 3'-PMNGL-5' associated with the 3'-NPMGL-5' wild-type VSV genome, where N is the gene encoding nucleocapsid protein, P is the gene encoding phosphoprotein, M is the gene encoding matrix protein, G is the gene encoding attachment glycoprotein, and L is the gene encoding RNA-dependent polymerase protein. 80. Immunosuppressive compound of claim 74 consisting of a selected mutant genome from a pool comprising '-PNMGct-1)L-5', 3'-PNMG(ct-9)L-5', 3'-PMNG(ct-1)L-5', and 3'-PMNG(ct-9)L-5', where N is the gene encoding nucleocapsid protein, P is the gene encoding phosphoprotein, M is the gene encoding matrix protein, G(ct-1) is the gene encoding attachment glycoprotein with twenty-eight post-carboxy amino acid deletions, G(ct-9) is the gene encoding attachment glycoprotein with twenty post-carboxy amino acid deletions, and L is the gene encoding RNA-dependent polymerase protein. 81. Immunosuppressive mixture of claim 80 where the mutant genome is 3'-PNMG(ct-1)L-5'. 82. Immunosuppressive mixture of claim 80 where the mutant genome is 3'-PNMG(ct-1)L-5'. 83. An immunogenic compound of claim 80, which is further comprised of a third type of mutation in its genome, where the mutation is a ts mutation, a site mutation, an ambisense RNA mutation, a deletion mutation, an insertion mutation, or a non-cytopathic M mutation. 84. Immunostimulatory mixture of claim 71 where foreign RNA is selected from the group. Containing the genes of HIV, HTLV, SIV, PIV, HSV, CMV, Epstein-Barr virus, varicella-zoster virus, mumps virus, measles virus, influenza virus, poliovirus, rhinovirus, hepatitis A virus, hepatitis B virus, hepatitis C virus, Norwalk virus, togavirus, alphavirus, rubella virus, rabies virus, Marburg virus, Ebola virus, papillomavirus, polyoma virus, metabnemiovirus, coronavirus, vibriozolera, streptococcus pneumoniae, streptococcus pyogenes, and others. Helicobacter pylori gene, Streptococcus agalactia gene, Nisseria meningitidis gene, Nisseria gonorrhoea gene, Corine bacterium dipteria gene, Clostridium tetanis gene, Bordetellaper tussis gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, cytokine encoding genes, T epitope encoding genes, CTL epitope encoding genes, complementary encoding genes, and cofactor encoding genes. 85. Immunosuppressive mixture of claim 84 where HIV gene is selected from a group consisting of gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 86. Immunosuppressive mixture of claim 85, where the HIV gene is gag. 87. Immunosuppressive mixture of claim 86 where the mutant genome is 3'-gag1-PNMG(ct-1)L-5', 3'-gag1-PNMG(ct-9)L-5', 3'-gag1-PMNG(ct-1)L-5', 3'-gag1-PMNG(ct-9)L-5', 3'-PNMG(ct-1)L-gag5-5', 3'-PNMG(ct-9)L-gag5-5', 3'-PMNG(ct-1)L-gag5-5' or 3'-PMNG(ct-9)L-gag5-5'. 88. Immunosuppressive mixture of claim 71, whereby the mixture is administered by a choice of routes comprising intravenous, intradermal, subcutaneous, intramuscular, peritoneal, oral, rectal, nasal, buccal, vaginal and external routes. 89. An immunogenic mixture of claim 71 where the two mutations are a cut G gene mutation and a non-cytopathic M gene mutation. 90. An immunogenic mixture of claim 89 where the transduced G protein by the truncated G gene has a deletion of twenty-eight post-carboxylic acid amino acids. 91. Immunosuppressive compound of claim 89 where the G protein encoded by the truncated G gene has a cytoplasmic tail domain consisting of one amino acid set. 92. Immunosuppression compound of claim 89 where the non-cytopathic mutation of gene M (M(ncp)) is the mutation of methionine 33 and methionine 51 of gene M. 93. An immunogenic mixture of claim 89 consisting of a mutant genome of 3'-NPM(ncp)G(ct-1)L-5' or 3'-NPM(ncp)G(ct-9)L-5'. 94. The immunogenicity mixture of claim 89, which is further comprised of a third type of mutation in its genome, where the mutations are ts mutations, site mutations, gene swap mutations, G-stem mutations, ambisense RNA mutations, G-insertion mutations, and gene deletion mutations. 95. Immunosuppressive mixture of claim 89 where foreign RNA is selected from a group comprising the following genes: HIV, HTLV, SIV, PIV, HSV, CMV, Epten-Barr virus, Varicella-Zoster virus, Mumps virus, Measles virus, Influenza virus, Poliovirus, Rhinovirus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Norwalk virus, Tokavirus, Alphavirus, Rubella virus, Rabies virus, Marburg virus, etc. Ebola virus genes, Papilloma virus genes, Polyoma virus genes, Tabnema virus genes, Coronavirus genes, Vibrio solera genes, Streptococcus pneumoniae genes, Streptococcus pyogenes genes, Helitobacter pylori genes, Streptococcus agalactiae genes, Nisveria meningitidis genes, Nisseria gonorrhoea genes, Corine bacterium dipteris genes, Clostridium tetanus genes, Boretel lapiotracystis genes, Haemophilus genes, Chlamydia genes, Escherichia coli genes, genes encoded in zidodine, genes encoded in helper epitopes T, genes encoded in epitopes CTL, genes encoded in complementary genes, and genes encoded in cofactors. 96. Immunosuppressive combination of claim 95, whereby HIV immunity is selected from a group consisting of gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 97. The immunogenic compound of claim 96 is gag. 98. Immunosuppressive mixture of claim 97 where the mutant genome is 3'-gag1-NPM(ncp)G(ct-1)L-5'3'-gag1-NPM(ncp)G(ct-9)L-5',3'-NPM(ncp)G(ct-1)gag5-5' or 3'-NPM(npm)G(ct-g)gag5-5'. 99. Immunosuppressive compound of claim 71 where the two mutations are the ts N (N(ts)) mutation and the ts L (L(ts)) mutation. 100. Immunosuppressive mixture of claim 99 containing a mutant genome of 3'-N(ts)PMGL(ts)-5'. 101. The immunogenicity of claim 99 is further comprised of three types of mutations in its genome, namely: site mutation, transposition mutation, G-stem mutation, non-cytopathic M gene mutation, ambisense RNA mutation, G gene truncation mutation, G gene insertion mutation, and gene deletion mutation. 102. Immunosuppressive mixture of claim 99 where foreign RNA is selected from a group comprising the following genes: HIV, HTLV, SIV, PIV, HSV, CMV, Epsden-Ber virus, Varicella-Sauder virus, Mumps virus, Epsden-Influenza virus, Poliovirus, Rhinovirus, Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, Norwalk virus, Tokavirus, Alphavirus, Rubella virus, Rabies virus, Marburg virus, Ebola virus, Papillomavirus, Poliovirus, Metapneumovirus, and Coronavirus. Virus, Vibrio solera gene, Streptococcus pneumoniae gene, Streptococcus pyogenes gene, Hecobacter pylori gene, Streptococcus agalactia gene, Nisseria meningitis gene, Nisseria gonorrhoea gene, Corine bacterium dipteris gene, Clostridium tetanus gene, Bordetella purpura gene, Haemophilus gene, Chlamydia gene, Escherichia coli gene, cytodine encoding gene, T epitope encoding gene, CTL epitope encoding gene, complementary encoding gene, and cofactor encoding gene. 103. Immunosuppressive mixture of claim 102 where HIV gene is selected from a group consisting of gag, env pol, vif, nef, tat, vpr, rev, or vpu. 104. Immunosynthetic mixture of claim 103, where the gene is gag. 105. Immunosuppression mixture of claim 104 where the mutant genomes are 3,-gag1-N(ts)PMGL(ts)L-5' and 3'-N(ts)PMGL(ts)L-gag5-5'. 106. Immunosuppression mixture of claim 71 where the two vector mutations are the G(stem) mutation and the gene swap mutation. 107. Immunosuppressive mixture of claim 106 where the mutant vector genome is 3'-gag-NPMG(stem)L-5'. 108. The immunogenicity mixture of claim 106, which is further comprised of a third type of mutation in its genome, where the mutation is a site mutation, ts mutation, gene swap mutation, non-cytopathic M gene mutation, ambisense RNA mutation, truncated G gene mutation, G gene insertion mutation, and gene deletion mutation. 109. Vector of claim 108 where foreign RNA is selected from a group comprising HIV gene, HTLV gene, SIV gene, PIV gene, HSV gene, CMV gene, Epden-Barr virus gene, Varicella-Zoster virus gene, Mumps virus gene, Measles virus gene, Influenza virus gene, Poliovirus gene, Rhinovirus gene, Hepatitis A virus gene, Hepatitis B virus gene, Hepatitis C virus gene, Norwalk virus gene, Toka virus gene, Alpha virus gene, Rubella virus gene, Rabies virus gene, Marburg virus gene, Ebola virus gene, Papilloma virus gene, Polyoma virus gene, Metapneumovirus gene, Coronavirus gene, Vibrio solera gene, etc. Streptococcus pneumoniae gene, Streptococcus pyogenes gene, Helicobacter pylori gene, Streptococcus agalactia gene, Nisseria meningitidis gene, Nisseria gonorrhoea gene, Corine bacterium dipteris gene, Clostridium tetanus gene, Bordetella pertussis gene, Haemophilus gene, Chlamydia gene, Essericia coli gene, Zidocoenzyme gene, Helper epitope T gene, CTL epitope gene, Supplemental epitope gene, and Cofactor epitope gene. 110. An immunogenic treatment method for mammalian hosts against bacterial infection is employed, consisting of administering an immunogenic dose of a genetically modified VSV vector containing (a) at least two different mutations in its genome, selected from a group comprising ts mutations, spot mutations, transposition mutations, G-stem mutations, non-cytopathogenic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G gene insertion mutations, and deletion mutations, where two mutations synergistically attenuate VSV pathogenesis; and (b) at least one foreign RNA sequence inserted into or replacing regions of the VSV genome not required for replication, where the RNA encodes selected bacterial proteins from a group comprising Vibrio solera protein, Streptococcus pneumoniae protein, Streptococcus pyogenase protein, Streptococcus agalactia protein, and others. Helicobacter pylori protein, Nisseria meningitidis protein, Nisseria gonorrhoea protein, Corine bacterium dipteris protein, Clostridium tetanus protein, Bordetella pertussis protein, Haemophilus protein, Chlamydia protein, Escherichia coli protein. 111. Method of claim 110 where two mutations are a cut gene G mutation and a gene N swap mutation. 112. The method of claim 111, where the G protein encoded by the truncated G gene has twenty deletions of the last carboxylic acid amino acids. 113. The method of claim 111, where the G protein encoded by the truncated G gene has twenty-eight deletions of the post-carboxylic acid endings. 114. Method of claim 111 where protein G encoded by the cleavage gene G has a cytoplasmic tail domain consisting of a single set of amino acids. 115. The method of claim 111, where the G protein encoded by the truncated G gene has a cytoplasmic tail domain composed of nine amino acids. 116. Method of claim 111 where the mutant genome is 3'-PNMGL-5' or 3'-PMNGL-5' is related to the VSV 3'-NPMGL-5' wild-type genome. 117. The method of claim 111 consists of a selected mutant genome from a group comprising 3'-PNMG(ct-1)L-5', 3'-PNMG(ct-9)L-5', 3'-PMNG(ct-1)L-5', and 3'-PMNG(ct-9)L-5'. 118. The method of claim 103, which is further comprised of a third type of mutation in its genome, where the mutation is a ts mutation, a site mutation, an ambisense RNA mutation, a gene deletion mutation, a gene insertion mutation, or a non-cydopathic M gene mutation. 119. An immunogenic approach for mammalian hosts against viral infection consisting of administering an immunogenic dose of a genetically modified VSV vector comprising (a) at least two different types of mutations in its genome—selectable mutations from a group comprising ts mutations, spot mutations, transposition mutations, G-stem mutations, non-cytopathogenic M gene mutations, ambisense RNA mutations, truncated G gene mutations, G gene insertion mutations, and deletion mutations—two of which synergistically attenuate VSV pathogenesis; and (b) at least one foreign RNA sequence inserted into or replacing regions of the VSV genome not required for replication, where the RNA encodes a selected viral protein. From a group consisting of HIV virus protein, HTLV virus protein, SIV virus protein, RSV virus protein, PIV virus protein, HSV virus protein, CMV virus protein, Epden-Barr virus protein, Varicella-Zoster virus protein, Mumps virus protein, Measles virus protein, Influenza virus protein, Poliovirus protein, Rhinovirus protein, Hepatitis A virus protein, Hepatitis B virus protein, Hepatitis C virus protein, Norwalk virus protein, Tokavirus protein, Alphavirus protein, Rubella virus protein, Rabies virus protein, Marburg virus protein, Ebola virus protein, Papillomavirus protein, Polyoma virus protein, Tabebuia pneumovirus protein, and Coronavirus protein. 120. Method of claim 119 where RNA is an HIV gene selected from a group consisting of gag, env, pol, vif, nef, tat, vpr, rev, or vpu. 121. Method of claim 119, where HIV is a gag. 122. Method of claim 119 where two mutations are a truncated G gene mutation and an N gene swap mutation. 123. The method of claim 122, where the G protein encoded by the truncated G gene has twenty deletions of the last carboxylic acid amino acids. 124. The method of claim 122, where the G protein encoded by the truncated G gene has twenty-eight deletions of the last carciate amino acids. 125. The method of claim 122, where the G protein encoded by the cleavaged G gene has a cytoplasmic tail domain consisting of a single set of amino acids. 126. The method of claim 122, where the G protein encoded by the truncated G gene has a cytoplasmic tail domain composed of nine amino acids. 127. Method of claim 111 where gene N swapped with 3'-PNMGL-5' or 3'-PMNG-5' is associated with a 3'-NPMGL-5' wild-type VSV genome. 128. The method of claim 122 consists of a selected mutant genome from a group containing 3'-PNMG(ct-1)L-5', 3'-PNMG(ct-9)L-5', 3'-PMNG(ct-1)L-5', and 3'-PMNG(ct-9)L-5'. 129. The method of claim 122, which consists of three types of mutations in its genome, where the mutation is a ts mutation, a site mutation, an ambisense RNA mutation, a gene deletion mutation, a gene insertion mutation, or a non-cytopathic M gene mutation. 130. Method of claim 122 where the mutant genome is 3'-gag1-PNMG(ct-1)L-5',3'-gag1-PNMG(ct-9)L-5',3'-gag1-PMNG(ct-1)L-5',3'-gag1-PMNG(ct-9)L-5',3'-PNMG(ct-1)L-gag5-5',3'-PNMG(ct-9)L-gag5-5',3'-PMNG(ct-1)L-gag5-5', or 3'-PMNG(ct-9)L-gag5-5'. 131. The method of claim 119 where the two mutations are a cut mutation of the G gene and a non-cytopathic mutation of the M gene. 132. The method of claim 131, where the G protein encoded by the truncated G gene has twenty deletions of the post-carboxylic acid terminals. 133. The method of claim 131, where the G protein encoded by the truncated G gene has a cytoplasmic tail domain composed of a set of amino acids. 134. The method of claim 131, where the non-cytopathic (M(ncp)) mutation of the M gene is the mutation at methionine 33 and methionine 51 of the M gene. 135. The method of claim 131, which is further comprised of a mutant genome of 3'-npm(ncp)G(ct-1)L-5' or 3'-NPM(ct-9)L-5'. 136. The method of claim 123, which is further comprised of three types of mutations in its genome, where the mutations are ts mutations, spot mutations, gene swapping mutations, G-stem mutations, ambisense RNA mutations, G-insertion mutations, and gene deletion mutations. 137. Method of claim 123 where the mutant VSV genome is 3'-gag1-NPM(ncp)G(ct-1)L-5'3'-gag1-NPM(ncp)G(ct-9)L-5',3'-NPM(ncp)G(ct-1)gag5-5' or 3'-NPM(npm)G(ct-g)gag5-5' 138. The method of claim 119 where the two mutations are the mutation of the gene ts N (N(ts)) and the mutation of the gene ts L (L(ts)). 139. The method of claim 138, which is further comprised of the mutant genome of 3'-N(ts)PMGL(ts)L-5' 140. The method of claim 138, which is further comprised of three types of mutations in its genome, where the mutation is a site mutation, a gene swap mutation, a G-stem mutation, a boncytopathic M gene mutation, an ambisense RNA mutation, a truncated G gene mutation, a G gene insertion mutation, or a gene deletion mutation. 141. Method of claim 119 where the mutant genome is 3'-gag1-N(ts)PMGL(ts)L-5' or 3'-N(ts)PMGL(ts)-gag5-5, 142. The method of claim 119 where the two mutations are the G (stem) mutation and the transposition mutation. 143. Method of claim 142 where the mutant genome is 3'-gag1-NPMG(stem)L-5'. 144. The method of claim 142, which is further comprised of a third type of mutation in its genome, where the mutation is a site mutation, a ts mutation, a gene swap 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.