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DNA sequence coding for cholera toxin subunits, expression in microbial host cells; use in vaccine production
Patent report and the transformant grown to express the corresponding peptide. The peptides may also be synthesized and coupled to e.g. serum albumins and the resulting immunogens may be formulated as vaccines. 034-84
Protecting domestic chickens against avian leukosis virus, Marek's disease vaccine prepared by'extracting antigen of Progenitor cryptocides Livingston-Wheeler V US 4,410,510; 18 October 1983 Domestic chickens are protected against avian leukosis virus by culturing Progenitor cryptocides ATCC 31874. which is isolated from a warm-blooded animal carrying a malignant tumor or from the tumor itself. The microorganism is able to synthesize chorionic gonadotropin in its stable form or in its alpha and beta subunits. The culture medium containing cells is boiled to dissolve the soluble portion of the microorganism, including the cell wall, to release the watersoluble antigen. The heat denatured protein layer is discarded. Methanol or preferably ethanol may be used to precipitate the antigen from the remaining liquid. The antigen stimulates the immune response in chickens to avian leukosis and can be used to prevent Marek's disease, 035-84
Temperature sensitive recombinant equine influenza virus, containing human influenza virus genes; useful as vaccine CornelI-Res Found. World 8303-546; 28 October 1983 A new temperature sensitive virus able to provide an equine influenza (El) vaccine, is a reassortant mutant formed by mating a wild-type El virus with a chemically mutagenized, temperature sensitive h u m a n influenza (HI) virus. It contains at least one temperature sensitive gene and at least 2 but not more than 6, HI-derived genes. The virus especially contains 6EI and 2HI viral genes, and can be used to protect animals against E1 infection. The virus has a temperature shut-off at 37-39°C so produces only mild symptoms while producing effective protection. Cells are infected with both parent viruses, then reassortant viruses plated on monolayer cultures at the permissive temperature in presence of antiserum against the temperature-sensitive parent. The virus in the plaques is inoculated into tissue cultures, incubated at the permissive temperature and harvested. The desired reassortant is then passaged twice and grown in tissue culture. 036-84
Rabies antigenic protein expression in vectors for the preparation of vaccine Transgene Eur. 94-887; 23 November 1983 An expression vector for rabies antigenic protein contains ( 1) a D N A sequence corresponding wholly or partially to the effective D N A coding sequence for rabies antigens, and (2) a promoter for the expression of this sequence in Escherichia coli or Bacillus subtilis. Preferred fragments of the rabies gene are those between the restriction sites H i n d l l l - H i n d l l l , H i n d l I I - A o s l I and H i n d l l l - N r u I . Preferably, the effective partial D N A sequence comprises the total D N A sequence limited at the 5' end by a H i n d l l I site. The vectors contain the whole or part of phage MI3 and a l a m b d a phage promoter site. Alternatively, the vectors may be bacterial plasmids containing a l a m b d a phage promoter, such as PI, and a translation initiation region, such as the l a m b d a c l l r b s region. The vector should also contain a translation antitermination function, such as the l a m b d a W gene. The promoter is controlled by a repressor. The vector is used to transform E. coil or B. subtilis to produce the rabies antigen, which is used as an anti-rabies vaccine. 037-84
164
Vaccine, Vol. 2, June 1984
Vaccine against bovine mastiffs, containing Staphylococcus aureus and Streptococcus agalactiae antigens Cornell-Res. Found. Eur. 94-997:31 November 1983 A vaccine against bovine mastitis comprises, as the active components, at least 1 each of (1) encapsulated Staphylococcus aureus antigen, (2) unencapsulated S. aureus antigen, and (3)Streptococcus agalactiae antigen of type (a, b and/or c), II or Ill. (l) Is prepared by culturing a cattle-isolated S. aureus strain in an appropriate medium and (a) inactivating the ceils, or (b) recovering the cells, inactivating them and separating the antigen, or (c) recovering the cells, separating the antigen and inactivating the antigen, or (d) recovering the cells, concentrating the antigen and inactivating the antigen. (2) Is prepared by culturing a cattle-derived strain, separating and inactivating the antigen. (3) Is prepared from a cattlederived strain by growing the cells, harvesting them, recovering and inactivating the antigen, and mixing it with an adjuvant. The vaccines are administered to cattle at least twice at an interval of about 3 weeks. 038-84
DNA sequence coding for cholera toxin subunits, expression in microbial host cells; use in vaccine production SK + F - R I T Eur. 95-452; 30 November 1983 Digestion of D N A from a toxin-producing strain of Vibrio cholerae with ClaI produces 2 genes, each coding for 1 subunit of cholera toxin. These are isolated by hybridization with eltA or eltB probes. The resulting fragment is inserted into a ClaI-digested vector, specifically pBR322 for cloning a single gene, or pBR327 for cloning both genes together. The resulting recombinant plasmid is used to transform host cells, e.g. Escherichia coli KI2, or a non-toxin producing V. cholerae strain. The transformants express toxin subunits A and/orB. These are useful in vaccine production. Subunit A must first be converted to an toxoid, e.g. by treating with glutaraldehyde, and the same treatment may also be applied to subunit B. 039-84
Antigenic compositions for treatment of neoplastic diseases prepared by selective recombination-hybridization of DNA RNA and histone fractions for vaccine preparation DSO Pharmachim US 4,415,553; 15 November 1983 A cancer-active single strand DNA(I), a cancer-active RNA (2) and an arginine-rich histone fraction (3) are isolated from the cell nuclei of neoplastic animal tissue. At least one other portion of the cell nuclei is deaggregated by enzymatic treatment with pepsin and a lysine-rich histone fraction (4) is obtained. Fractions (I), (2) and (4) are recombined in the presence of streptomycin-cysteine and mixed with fraction (3). The tissue used can be of human origin or obtained from tumors transplanted into animals or from virus-, chemically-, irradion-caused tumors in animals. A major objective of the invention is to provide methods by which new nucleoproteins with varying and specific antigenic properties can be produced from histone fractions, single-stranded D N A and active RNA isolated from animal cancer cell nuclei. 040-84
Hepatitis B surface antigen (HBsAG) preparation, vaccine preparation; tissue culture extraction Merck-USA US 4,416,986; 22 November 1983 Hepatitis B surface antigen (HBsAG) is prepared by growing cells which shed HBsAG in the presence of a nutrient medium on hollow fibre capillary units of M W cut-off about
Protecting domestic chickens against avian leukosis virus, Marek's disease vaccine prepared by'extracting antigen of Progenitor cryptocides Livingston-Wheeler V US 4,410,510; 18 October 1983 Domestic chickens are protected against avian leukosis virus by culturing Progenitor cryptocides ATCC 31874. which is isolated from a warm-blooded animal carrying a malignant tumor or from the tumor itself. The microorganism is able to synthesize chorionic gonadotropin in its stable form or in its alpha and beta subunits. The culture medium containing cells is boiled to dissolve the soluble portion of the microorganism, including the cell wall, to release the watersoluble antigen. The heat denatured protein layer is discarded. Methanol or preferably ethanol may be used to precipitate the antigen from the remaining liquid. The antigen stimulates the immune response in chickens to avian leukosis and can be used to prevent Marek's disease, 035-84
Temperature sensitive recombinant equine influenza virus, containing human influenza virus genes; useful as vaccine CornelI-Res Found. World 8303-546; 28 October 1983 A new temperature sensitive virus able to provide an equine influenza (El) vaccine, is a reassortant mutant formed by mating a wild-type El virus with a chemically mutagenized, temperature sensitive h u m a n influenza (HI) virus. It contains at least one temperature sensitive gene and at least 2 but not more than 6, HI-derived genes. The virus especially contains 6EI and 2HI viral genes, and can be used to protect animals against E1 infection. The virus has a temperature shut-off at 37-39°C so produces only mild symptoms while producing effective protection. Cells are infected with both parent viruses, then reassortant viruses plated on monolayer cultures at the permissive temperature in presence of antiserum against the temperature-sensitive parent. The virus in the plaques is inoculated into tissue cultures, incubated at the permissive temperature and harvested. The desired reassortant is then passaged twice and grown in tissue culture. 036-84
Rabies antigenic protein expression in vectors for the preparation of vaccine Transgene Eur. 94-887; 23 November 1983 An expression vector for rabies antigenic protein contains ( 1) a D N A sequence corresponding wholly or partially to the effective D N A coding sequence for rabies antigens, and (2) a promoter for the expression of this sequence in Escherichia coli or Bacillus subtilis. Preferred fragments of the rabies gene are those between the restriction sites H i n d l l l - H i n d l l l , H i n d l I I - A o s l I and H i n d l l l - N r u I . Preferably, the effective partial D N A sequence comprises the total D N A sequence limited at the 5' end by a H i n d l l I site. The vectors contain the whole or part of phage MI3 and a l a m b d a phage promoter site. Alternatively, the vectors may be bacterial plasmids containing a l a m b d a phage promoter, such as PI, and a translation initiation region, such as the l a m b d a c l l r b s region. The vector should also contain a translation antitermination function, such as the l a m b d a W gene. The promoter is controlled by a repressor. The vector is used to transform E. coil or B. subtilis to produce the rabies antigen, which is used as an anti-rabies vaccine. 037-84
164
Vaccine, Vol. 2, June 1984
Vaccine against bovine mastiffs, containing Staphylococcus aureus and Streptococcus agalactiae antigens Cornell-Res. Found. Eur. 94-997:31 November 1983 A vaccine against bovine mastitis comprises, as the active components, at least 1 each of (1) encapsulated Staphylococcus aureus antigen, (2) unencapsulated S. aureus antigen, and (3)Streptococcus agalactiae antigen of type (a, b and/or c), II or Ill. (l) Is prepared by culturing a cattle-isolated S. aureus strain in an appropriate medium and (a) inactivating the ceils, or (b) recovering the cells, inactivating them and separating the antigen, or (c) recovering the cells, separating the antigen and inactivating the antigen, or (d) recovering the cells, concentrating the antigen and inactivating the antigen. (2) Is prepared by culturing a cattle-derived strain, separating and inactivating the antigen. (3) Is prepared from a cattlederived strain by growing the cells, harvesting them, recovering and inactivating the antigen, and mixing it with an adjuvant. The vaccines are administered to cattle at least twice at an interval of about 3 weeks. 038-84
DNA sequence coding for cholera toxin subunits, expression in microbial host cells; use in vaccine production SK + F - R I T Eur. 95-452; 30 November 1983 Digestion of D N A from a toxin-producing strain of Vibrio cholerae with ClaI produces 2 genes, each coding for 1 subunit of cholera toxin. These are isolated by hybridization with eltA or eltB probes. The resulting fragment is inserted into a ClaI-digested vector, specifically pBR322 for cloning a single gene, or pBR327 for cloning both genes together. The resulting recombinant plasmid is used to transform host cells, e.g. Escherichia coli KI2, or a non-toxin producing V. cholerae strain. The transformants express toxin subunits A and/orB. These are useful in vaccine production. Subunit A must first be converted to an toxoid, e.g. by treating with glutaraldehyde, and the same treatment may also be applied to subunit B. 039-84
Antigenic compositions for treatment of neoplastic diseases prepared by selective recombination-hybridization of DNA RNA and histone fractions for vaccine preparation DSO Pharmachim US 4,415,553; 15 November 1983 A cancer-active single strand DNA(I), a cancer-active RNA (2) and an arginine-rich histone fraction (3) are isolated from the cell nuclei of neoplastic animal tissue. At least one other portion of the cell nuclei is deaggregated by enzymatic treatment with pepsin and a lysine-rich histone fraction (4) is obtained. Fractions (I), (2) and (4) are recombined in the presence of streptomycin-cysteine and mixed with fraction (3). The tissue used can be of human origin or obtained from tumors transplanted into animals or from virus-, chemically-, irradion-caused tumors in animals. A major objective of the invention is to provide methods by which new nucleoproteins with varying and specific antigenic properties can be produced from histone fractions, single-stranded D N A and active RNA isolated from animal cancer cell nuclei. 040-84
Hepatitis B surface antigen (HBsAG) preparation, vaccine preparation; tissue culture extraction Merck-USA US 4,416,986; 22 November 1983 Hepatitis B surface antigen (HBsAG) is prepared by growing cells which shed HBsAG in the presence of a nutrient medium on hollow fibre capillary units of M W cut-off about