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Haemophilus influenzae type b protein conjugate vaccine comprising reductive amination production of oxidized polyribosylribitol-phosphate fragment and outer membrane protein
P a t e n t R e p o r t ..... 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. Non-reverting live Shigella vaccines: Shigella flexneri having a requirement for an essential metabolite which is not available in a mammalian host
Leland-Stanford-Jr. Univ. World 8909 063; 5 May 1989 The following are claimed: (a) a live Shigella strain having, as a result of a non-reverting mutation, a requirement for at least 1 essential metabolite not available in a mammalian host; (B) a live Shigella strain having the following properties: nonreverting aro D-, Sereny negative, Congo Red positive, serotype Y, sensitivity to antibiotics and ability to grow on chemically defined media; (C) a vaccine strain of Shigella flexneri which, as a result of a non-reverting deletion or deletion-inversion, has a requirement for at least one essential metabolite not available in a mammalian host, is sensitive to antibiotics and comprises the invasiveness plasmid; (D) Shigella flexneri strain S F L l l 4 (ATCC 53755). A vaccine strain of S. flexneri is produced by: (a) inserting a transposon encoding antibioticresistance into an aro gene ofS. flexneri; (b) selecting S. flexneri mutants which revert to antibiotic sensitivity; (c) screening the mutants for a deletion or deletion inversion; and (d) selecting non-reverting mutants which are Sereny negative and Congo Red positive. The method can be applied to other organisms. 036-90 Immunoprotective antigenic protein against pathogenic bacteria comprises active adenylate-cyclase; mouse monoclonal antibody
Inst. Pasteur I N S E R M Eur. 388 170; 25 October 1989 A protein (I) is claimed with a mol.wt of 43000+4300, a pI of 5.7-6.1 (especially 5.9), specifically recognized by polyclonal anti-adenylate-cyclase (AC, EC 4.6.1.1) antibodies raised against purified AC preparations, devoid of AC calmodulin activity (CAM), and devoid of affinity for CaM. A second protein (II) is claimed as for (I) but having a mol.wt of 90000. Proteins having antigenic cross-reactivity with (I) and (II) are new, having a different mol.wt such as obtainable from virulent or avirulent Bordetella parapertussis, Bacillus anthracis, Yersinia spp. and Pasteurella spp., and their variants. Monoclonal antibodies against any of the proteins are obtained by fusion of spleen lymphocytes from mice immunized with any of the purified proteins with a mouse myeloma cell line. The antibodies are used for passive immunization. The proteins are used for vaccination against B. parapertussis and Bordetella pertussis in humans or Bordetella bronchiseptica and Bordetella avium in animals. Vaccine administration may be by i.n., oral or parenteral routes. 037-90
Haemophilus influenzae type b protein conjugate vaccine comprising reductive amination production of oxidized polyribosylribitol-phosphate fragment and outer membrane protein Am. Cyanamid Eur. 338 265; 25 October 1989 An immunogenic polysaccharide-protein conjugate is claimed comprising the reductive amination production of: (a) an oxidized polyribosyl-ribitol-phosphate (PRP) polysaccharide
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fragment (I) derived from the capsular polysaccharide of Haemophilus influenzae type b; and (b) the outer membrane protein of H. influenzae type b having a mol.wt of 38 000 or 40000. Also claimed is a process for the isolation and purification of the 38 000 or 40000 protein. (I) is prepared by treating purified PRP polysaccharide with NA or potassium periodate, or periodic acid at 4-25°C in the dark, dialysing against pyrogen-free water or purifying by gel filtration and column chromatography, followed by concentrating and drying. The conjugate is prepared by mixing the major outer membrane protein and (I) to form Schiff base linkages, reducing the linkages with a suitable borohydride reducing agent and purifying the conjugate by gel filtration column chromatography or dialysis. The conjugate is used as a vaccine to elicit antibodies to PRP and the outer membrane protein of H. influenzae type b and causes immunity to invasive diseases caused by H. influenzae type b. 038-90
Purified recombinant gag precursor of HIV virus from yeast or insect expression system, useful as AIDS vaccine
Merck USA Eur. 340 837; 8 November 1989
Saccharomyces cerevisiae (and other yeast spp.) recombinant gag precursor (I) with > 9 5 % purity is claimed. (I) is preferably myristylated. Purification of (I) is achieved by: thawing frozen clarified yeast extract containing (I), expressed in a recombinant yeast expression system; precipitation by freezing for 24 h; pelleting by centrifugation and separating the pellet; mixing the pellet with a membrane solubilizing solution which also solubilizes undesired membrane-bound proteins; re-pelleting (I) by centrifugation and separating the pellet; dissolving the pellet in a (1)-solubilizing solution to yield the denatured pellet; subjecting the denatured pellet to hydrophobic interaction chromatography and isolating (I)-containing fractions yielding > 9 5 % pure (I). Preparations of (I) may be rendered water-soluble by subjecting the protein to reversephase HPLC or to gel filtration chromatography in organic phase. (I) in combination with a suitable immunological adjuvant is used as a vaccine. The yeast expression system is U9 no. 1-5. Recombinant gag precursor may be expressed in an insect expression system. 039-90
Fish vaccine against pathogenic bacteria containing live or killed avirulent, invasive immunogenic mutant strains of Vibrio
anguillarum Symbicom
World 8909 616; 19 October 1989 The following are claimed: (A) a live vaccine for immunization of fish against diseases caused by fish pathogens, which comprises an avirulent, invasive immunogenic mutant strain of a virulent pathogenic bacterium; the mutant strain may be from Vibrio anguillarum, Aeromonas hydrophilia, Cytophaga spp. or Pseudomonas spp.; (B) an avirulent, invasive, immunogenic mutant strain of a fish pathogenic bacterium for use as a live vaccine for the immunization of fish against diseases caused by fish pathogens; (C) a fish which is immunized with a live vaccine of (A); and (D) a vaccine for the immunization of fish against diseases caused by fish pathogens, which comprises a killed avirulent invasive, immunogenic strain of a fish pathogenic bacterium. The mutant strain may be a spontaneous mutant of pathogenic bacteria or may be produced by treatment with a mutagen. The avirulent mutant strain may be produced by
Leland-Stanford-Jr. Univ. World 8909 063; 5 May 1989 The following are claimed: (a) a live Shigella strain having, as a result of a non-reverting mutation, a requirement for at least 1 essential metabolite not available in a mammalian host; (B) a live Shigella strain having the following properties: nonreverting aro D-, Sereny negative, Congo Red positive, serotype Y, sensitivity to antibiotics and ability to grow on chemically defined media; (C) a vaccine strain of Shigella flexneri which, as a result of a non-reverting deletion or deletion-inversion, has a requirement for at least one essential metabolite not available in a mammalian host, is sensitive to antibiotics and comprises the invasiveness plasmid; (D) Shigella flexneri strain S F L l l 4 (ATCC 53755). A vaccine strain of S. flexneri is produced by: (a) inserting a transposon encoding antibioticresistance into an aro gene ofS. flexneri; (b) selecting S. flexneri mutants which revert to antibiotic sensitivity; (c) screening the mutants for a deletion or deletion inversion; and (d) selecting non-reverting mutants which are Sereny negative and Congo Red positive. The method can be applied to other organisms. 036-90 Immunoprotective antigenic protein against pathogenic bacteria comprises active adenylate-cyclase; mouse monoclonal antibody
Inst. Pasteur I N S E R M Eur. 388 170; 25 October 1989 A protein (I) is claimed with a mol.wt of 43000+4300, a pI of 5.7-6.1 (especially 5.9), specifically recognized by polyclonal anti-adenylate-cyclase (AC, EC 4.6.1.1) antibodies raised against purified AC preparations, devoid of AC calmodulin activity (CAM), and devoid of affinity for CaM. A second protein (II) is claimed as for (I) but having a mol.wt of 90000. Proteins having antigenic cross-reactivity with (I) and (II) are new, having a different mol.wt such as obtainable from virulent or avirulent Bordetella parapertussis, Bacillus anthracis, Yersinia spp. and Pasteurella spp., and their variants. Monoclonal antibodies against any of the proteins are obtained by fusion of spleen lymphocytes from mice immunized with any of the purified proteins with a mouse myeloma cell line. The antibodies are used for passive immunization. The proteins are used for vaccination against B. parapertussis and Bordetella pertussis in humans or Bordetella bronchiseptica and Bordetella avium in animals. Vaccine administration may be by i.n., oral or parenteral routes. 037-90
Haemophilus influenzae type b protein conjugate vaccine comprising reductive amination production of oxidized polyribosylribitol-phosphate fragment and outer membrane protein Am. Cyanamid Eur. 338 265; 25 October 1989 An immunogenic polysaccharide-protein conjugate is claimed comprising the reductive amination production of: (a) an oxidized polyribosyl-ribitol-phosphate (PRP) polysaccharide
290
Vaccine, Vol. 8, June 1990
fragment (I) derived from the capsular polysaccharide of Haemophilus influenzae type b; and (b) the outer membrane protein of H. influenzae type b having a mol.wt of 38 000 or 40000. Also claimed is a process for the isolation and purification of the 38 000 or 40000 protein. (I) is prepared by treating purified PRP polysaccharide with NA or potassium periodate, or periodic acid at 4-25°C in the dark, dialysing against pyrogen-free water or purifying by gel filtration and column chromatography, followed by concentrating and drying. The conjugate is prepared by mixing the major outer membrane protein and (I) to form Schiff base linkages, reducing the linkages with a suitable borohydride reducing agent and purifying the conjugate by gel filtration column chromatography or dialysis. The conjugate is used as a vaccine to elicit antibodies to PRP and the outer membrane protein of H. influenzae type b and causes immunity to invasive diseases caused by H. influenzae type b. 038-90
Purified recombinant gag precursor of HIV virus from yeast or insect expression system, useful as AIDS vaccine
Merck USA Eur. 340 837; 8 November 1989
Saccharomyces cerevisiae (and other yeast spp.) recombinant gag precursor (I) with > 9 5 % purity is claimed. (I) is preferably myristylated. Purification of (I) is achieved by: thawing frozen clarified yeast extract containing (I), expressed in a recombinant yeast expression system; precipitation by freezing for 24 h; pelleting by centrifugation and separating the pellet; mixing the pellet with a membrane solubilizing solution which also solubilizes undesired membrane-bound proteins; re-pelleting (I) by centrifugation and separating the pellet; dissolving the pellet in a (1)-solubilizing solution to yield the denatured pellet; subjecting the denatured pellet to hydrophobic interaction chromatography and isolating (I)-containing fractions yielding > 9 5 % pure (I). Preparations of (I) may be rendered water-soluble by subjecting the protein to reversephase HPLC or to gel filtration chromatography in organic phase. (I) in combination with a suitable immunological adjuvant is used as a vaccine. The yeast expression system is U9 no. 1-5. Recombinant gag precursor may be expressed in an insect expression system. 039-90
Fish vaccine against pathogenic bacteria containing live or killed avirulent, invasive immunogenic mutant strains of Vibrio
anguillarum Symbicom
World 8909 616; 19 October 1989 The following are claimed: (A) a live vaccine for immunization of fish against diseases caused by fish pathogens, which comprises an avirulent, invasive immunogenic mutant strain of a virulent pathogenic bacterium; the mutant strain may be from Vibrio anguillarum, Aeromonas hydrophilia, Cytophaga spp. or Pseudomonas spp.; (B) an avirulent, invasive, immunogenic mutant strain of a fish pathogenic bacterium for use as a live vaccine for the immunization of fish against diseases caused by fish pathogens; (C) a fish which is immunized with a live vaccine of (A); and (D) a vaccine for the immunization of fish against diseases caused by fish pathogens, which comprises a killed avirulent invasive, immunogenic strain of a fish pathogenic bacterium. The mutant strain may be a spontaneous mutant of pathogenic bacteria or may be produced by treatment with a mutagen. The avirulent mutant strain may be produced by