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New retrovirus of the HIV virus group is useful in diagnosis of HIV-1 and HIV-2 infections and in AIDS vaccine production
Patent Report This section provides information on worldwide patents relevant to vaccine design and production. The Patent Report gives the following information: title of patent, patentee, patent number, publication date and summary of the patent. A number of patents in this report are reproduced from 'Biotechnology Abstracts' with permission of Derwent Publications Ltd. Preparation of a pilus vaccine for cattle and pig obtained by cultivation of an adenine auxotrophic Escherichia coli mutant on a yeast extract culture medium
VEB lmpfstoffwerk-Dessau
of ,,~ 100 nm and detectable budding on the cell membrane. The virus includes the proteins p17, p24, p32, gp41, p52, p66, gp115 and gpl60, and gives a positive reaction with both HIV-1 and -2 positive sera. HIV-ODS positive sera react with gp41 (and its precursor gpl6); p18 and p24 (core proteins) and p53 and p66 (functional proteins). The virus is obtained by cocultivating infected lymphocytes with phytohaemagglutininstimulated donor lymphocytes in the presence of interleukin-2 and anti-interferon-a. It is then replicated in T4 + cells. 003-90
GDR 264 336; 1 February 1989 The preparation of pilus inoculants against Escherichia coil-caused infectious diseases of the digestive tract of cattle and pigs comprises cultivating the adenine auxotrophic E. coli mutant ZIMET 11086 (adhesion antigen K88), ZIMET 11087 (K99) or ZIMET 11088 (987p) using yeast extract as the culture medium and L-glutamic acid, L-aspartic acid, L-threonine, L-methionine and glycine as N-sources. The culture solution is then processed to give the inoculant which is used as a vaccine. The vaccine is prepared more cheaply than other pilus-based vaccines. The formation of the pilus on the cell surface is not absolutely necessary. Less biomass is needed to achieve an inoculant dose compared with previous processes, and the effect of the vaccine is not dependent on other antigen structures of the excitor cells. The vaccine is more effective than previous vaccines and gives a higher antibody titre. 001-90
Vaccine containing antisense nucleic acid to specific D N A or RNA of virus or oncogene; antiseose DNA and autisense RNA useful for AIDS or cancer diagnosis, therapy or prophylaxis
Theurer KE FRG 3742 049; 22 June 1989 A vaccine against virus diseases and cancer is prepared by synthesis (enzymatic or chemical) of retrogressive, mirrorimage, antisense nucleic acid corresponding to DNA or RNA of the virus genome or isolated oncogenes, or their fragments, which are useful for virus replication or pathogenicity. The antisense RNA or DNA is then replicated enzymatically in a cell-free system in the presence of a DNA-dependent replicase and nucleotides. The antisense DNA and RNA is useful for: (1) diagnosis of virus diseases or cancer, when labelled; or (2) prophylaxis or therapy, when incorporated into liposomes and modified to stimulate or inhibit intracellular replication or increase cell permeability. The vaccines have no side effects and are especially useful for control of AIDS. In an example, antisense DNA and RNA were prepared from proto-oncogenes or oncogenes, isolated from cancer cells. 002-90
New retrovirus of the HIV virus group is useful in diagnosis of HIV-1 and HIV-2 infections and in AIDS vaccine production
Habermehl KO FRG 3743 094; 29 June 1989 A new retrovirus and its fragments and extracts have the antigenic properties of HIV-ODS, ECACC V87111102. The virus is used: (a) to detect HIV-1 and HIV-2 infections and AIDS; and (b) to produce a vaccine against such conditions. It can be replicated to produce good yields of virus in monolayers of primary human macrophages, with less effect on cell viability compared with HIV-I. The new virus was isolated from a West African woman with lymphoadenopathy (CD4 population 500 Ill- 1; CD4/CD8 ratio 0.9). Electron microscopy shows it to have the characteristic HIV shape, with a diameter
92
Vaccine, Vol. 8, February 1990
Immunoprotective, genetically-detoxified pertussis toxin and vaccine with amino acid substitution(s) or deletion(s) produced by site-directed mutagenesis of toxin gene
Connaught Lab. Eur. 322 115; 28 June 1989 An immunoprotective, genetically-detoxified mutant of pertussis toxin, and a method for its production, are new. Vaccine against Bordetella pertussis comprises an effective amount of the mutant, or its toxoid, and an acceptable carrier. Conjugate vaccine comprises the mutant as carrier protein for a hapten, polysaccharide or polypeptide. Native B. pertussis 10536 TOX operon is new having a given DNA sequence and structural gene translation. More specifically, the mutant is characterized by genetic modification of the A portion (S1 subunit) of the toxin and/or the B portion of the toxin. Preferably (a) a single amino acid (e.g. Glu-129, Arg-58) is removed or replaced by Gly-129 or Glu-58, respectively; or (b) multiple amino acids are removed or replaced, e.g. Glu-129Tyr130 replaced by Gly- 129 Phe- 130, or Glu- 129/(S3)Tyr-92Lys-93 are replaced by Gly-129/(S3)Asn-92Arg-93. The B. pertussis strain is characterized in that the mutant gene comprises a clone numbered S-3036-2, S-3122-3-1, S-2962-1-1, S-2962-2-1 or S-3122-2-3. Residual activity is preferably <0.5% of that of the native toxin. 004--90
Attenuated microorganisms useful in vaccines have non-reverting mutation in two discrete genes in the aromatic biosynthetic pathway e.g. Salmonella typhi
Wellcome Eur. 322 237; 28 June 1989 An attenuated microorganism harboring a non-reverting mutation in each of two discrete genes in its aromatic biosynthetic pathway is claimed. Preferably the microorganism is a bacterial pathogen, especially an invasive organism. Preferably the microorganism is capable of expressing a heterologous antigen, and contains an expression cassette having DNA sequences encoding a structural gene of the heterologous antigen. A pharmaceutical composition containing the attenuated bacteria and an acceptable excipient is also claimed. More specifically, one of the non-reverting mutations occurs in the aroA gene and the second in the aroC, aroD or aroE genes. The microorganism is a Sahnonella,
Bordetella, Haemophilus, Leptospira, Streptococcus, Neisseria or M ycobacterium strain, preferably Salmonella typhimurium, S. typlfi, S. dublin or S. cholerasius. Specifically claimed is S. typhi strain Ty2 harboring either aroAaroC, aroAaroE, or aroAaroD non-reverting mutations. The mutants are safe and sufficiently immunogenic to raise an immune response. 005-90
VEB lmpfstoffwerk-Dessau
of ,,~ 100 nm and detectable budding on the cell membrane. The virus includes the proteins p17, p24, p32, gp41, p52, p66, gp115 and gpl60, and gives a positive reaction with both HIV-1 and -2 positive sera. HIV-ODS positive sera react with gp41 (and its precursor gpl6); p18 and p24 (core proteins) and p53 and p66 (functional proteins). The virus is obtained by cocultivating infected lymphocytes with phytohaemagglutininstimulated donor lymphocytes in the presence of interleukin-2 and anti-interferon-a. It is then replicated in T4 + cells. 003-90
GDR 264 336; 1 February 1989 The preparation of pilus inoculants against Escherichia coil-caused infectious diseases of the digestive tract of cattle and pigs comprises cultivating the adenine auxotrophic E. coli mutant ZIMET 11086 (adhesion antigen K88), ZIMET 11087 (K99) or ZIMET 11088 (987p) using yeast extract as the culture medium and L-glutamic acid, L-aspartic acid, L-threonine, L-methionine and glycine as N-sources. The culture solution is then processed to give the inoculant which is used as a vaccine. The vaccine is prepared more cheaply than other pilus-based vaccines. The formation of the pilus on the cell surface is not absolutely necessary. Less biomass is needed to achieve an inoculant dose compared with previous processes, and the effect of the vaccine is not dependent on other antigen structures of the excitor cells. The vaccine is more effective than previous vaccines and gives a higher antibody titre. 001-90
Vaccine containing antisense nucleic acid to specific D N A or RNA of virus or oncogene; antiseose DNA and autisense RNA useful for AIDS or cancer diagnosis, therapy or prophylaxis
Theurer KE FRG 3742 049; 22 June 1989 A vaccine against virus diseases and cancer is prepared by synthesis (enzymatic or chemical) of retrogressive, mirrorimage, antisense nucleic acid corresponding to DNA or RNA of the virus genome or isolated oncogenes, or their fragments, which are useful for virus replication or pathogenicity. The antisense RNA or DNA is then replicated enzymatically in a cell-free system in the presence of a DNA-dependent replicase and nucleotides. The antisense DNA and RNA is useful for: (1) diagnosis of virus diseases or cancer, when labelled; or (2) prophylaxis or therapy, when incorporated into liposomes and modified to stimulate or inhibit intracellular replication or increase cell permeability. The vaccines have no side effects and are especially useful for control of AIDS. In an example, antisense DNA and RNA were prepared from proto-oncogenes or oncogenes, isolated from cancer cells. 002-90
New retrovirus of the HIV virus group is useful in diagnosis of HIV-1 and HIV-2 infections and in AIDS vaccine production
Habermehl KO FRG 3743 094; 29 June 1989 A new retrovirus and its fragments and extracts have the antigenic properties of HIV-ODS, ECACC V87111102. The virus is used: (a) to detect HIV-1 and HIV-2 infections and AIDS; and (b) to produce a vaccine against such conditions. It can be replicated to produce good yields of virus in monolayers of primary human macrophages, with less effect on cell viability compared with HIV-I. The new virus was isolated from a West African woman with lymphoadenopathy (CD4 population 500 Ill- 1; CD4/CD8 ratio 0.9). Electron microscopy shows it to have the characteristic HIV shape, with a diameter
92
Vaccine, Vol. 8, February 1990
Immunoprotective, genetically-detoxified pertussis toxin and vaccine with amino acid substitution(s) or deletion(s) produced by site-directed mutagenesis of toxin gene
Connaught Lab. Eur. 322 115; 28 June 1989 An immunoprotective, genetically-detoxified mutant of pertussis toxin, and a method for its production, are new. Vaccine against Bordetella pertussis comprises an effective amount of the mutant, or its toxoid, and an acceptable carrier. Conjugate vaccine comprises the mutant as carrier protein for a hapten, polysaccharide or polypeptide. Native B. pertussis 10536 TOX operon is new having a given DNA sequence and structural gene translation. More specifically, the mutant is characterized by genetic modification of the A portion (S1 subunit) of the toxin and/or the B portion of the toxin. Preferably (a) a single amino acid (e.g. Glu-129, Arg-58) is removed or replaced by Gly-129 or Glu-58, respectively; or (b) multiple amino acids are removed or replaced, e.g. Glu-129Tyr130 replaced by Gly- 129 Phe- 130, or Glu- 129/(S3)Tyr-92Lys-93 are replaced by Gly-129/(S3)Asn-92Arg-93. The B. pertussis strain is characterized in that the mutant gene comprises a clone numbered S-3036-2, S-3122-3-1, S-2962-1-1, S-2962-2-1 or S-3122-2-3. Residual activity is preferably <0.5% of that of the native toxin. 004--90
Attenuated microorganisms useful in vaccines have non-reverting mutation in two discrete genes in the aromatic biosynthetic pathway e.g. Salmonella typhi
Wellcome Eur. 322 237; 28 June 1989 An attenuated microorganism harboring a non-reverting mutation in each of two discrete genes in its aromatic biosynthetic pathway is claimed. Preferably the microorganism is a bacterial pathogen, especially an invasive organism. Preferably the microorganism is capable of expressing a heterologous antigen, and contains an expression cassette having DNA sequences encoding a structural gene of the heterologous antigen. A pharmaceutical composition containing the attenuated bacteria and an acceptable excipient is also claimed. More specifically, one of the non-reverting mutations occurs in the aroA gene and the second in the aroC, aroD or aroE genes. The microorganism is a Sahnonella,
Bordetella, Haemophilus, Leptospira, Streptococcus, Neisseria or M ycobacterium strain, preferably Salmonella typhimurium, S. typlfi, S. dublin or S. cholerasius. Specifically claimed is S. typhi strain Ty2 harboring either aroAaroC, aroAaroE, or aroAaroD non-reverting mutations. The mutants are safe and sufficiently immunogenic to raise an immune response. 005-90