vaccine comprising non-infectious herpes virus particles; virion assembly-deficient ts 1201 mutant...

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  • This section provides information on worldwide pa~tents 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, Rochdale House, 128 Theobalds Road, London WC1X 8RD, UK. Telephone 071 242 5823; Fax 071 405 3630.

    Recombinant vaccinia virus expressing carcinoembryonic antigen on infected cell surface; vector for recombinant vaccine construction, and use in carcinoma therapy U.S. Dept. Health Human Serv. World 9219 266; 12 November 1992

    A recombinant virus (I) is claimed which comprises a vaccinia virus (VV) into which a carcinoembryonic antigen (CEA) gene is inserted. (I) expresses CEA on the surface of infected cells, and elicits an immune response in vivo against CEA and CEA-expressing cells. Also claimed is a recombinant virus (II) comprising a virus selected from baculovirus, Salmonella virus, human adenovirus, SV40 virus and cattle papilloma virus, into which the CEA gene is inserted, and having the same properties as (I). The VV may be a V-WR or a NYC strain, or may be recombined with another attenuated human VV strain. The CEA comprises a single or multiple immunodominant T-lymphocyte epitope. The virus preferably contains a promoter that increases CEA expression, and is preferably a recombinant CEA/VV designated rV-CEA (ATCC VR 2323). The virus can be used in the therapy of carcinomas expressing CEA, e.g. gastrointestinal, mamma, pancreas, bladder, ovary, lung or prostate carcinomas, or epithelial-derived carcinomas. It may also be used to stimulate the immune system against CEA to prevent the establishment and growth of carcinoma cells. 041-93

    Recombinant luliberin protein and analogue producing luliberin- specific antibody; used as a recombinant immunocastration vaccine for human, livestock and domestic animal CSL World 9219 746; 12 November 1992

    A recombinant protein comprises a protein sequence (PS) corresponding to luliberin (or an analogue), one or more T-lymphocyte epitopes and a purification site. It is capable of stimulating an immune response in an animal against luliberin. Also new are: (1) a recombinant immunocastration vaccine for use in mammal comprising (I) and at least one pharmaceutically acceptable carriers and/or diluents; and (2) a method for the immunocastration of an animal comprising administering an effective amount of (I) under conditions to generate luliberin-specific antibodies in the animal. The PS of (I) corresponds to at least two copies of luliberin and/or an analogue. The purification site is naturally occurring in the molecule and is preferably a glutathione-binding site on glutathione-S-transferase; or it is located on the pertussis toxin, pertussis toxoid or cholera-B toxin. It comprises hexa-histidine residues and the T-lymphocyte epitope occurs as a normal component in (I). The PS may also comprise residues allowing the protein to assemble into a virion-like structure. The protein may be used as a recombinant vaccine for domestic and wild animals. 042-93

    Patent Report Attenuated poliovirus; attenuation by 5'-noncoding region site-directed mutagenesis for use as a recombinant vaccine Almond JW AU 9176 128; 15 October 1992

    A novel attenuated poliovirus contains, in its 5'-coding region, the 5'-noncoding region of poliovirus type 3 Leon strain, or another poliovirus, modified by insertion of U and A at positions 472 and 537, respectively, or corresponding positions. The virus may be of type 1, 2 or 3. The attenuated virus is produced by: subcloning a portion of a poliovirus cDNA, including positions 472 and 537 (or corresponding positions); mutating positions 472 and 537 to U and A, respectively; reintroducing the mutated portion or a fragment into the complete cDNA from which it was derived; and obtaining a live virus from the cDNA. The attenuated poliovirus may be used as a recombinant vaccine. The mutations attenuate the virulence of wild-type viruses, and can attenuate existing live attenuated vaccine virus strains, making them less likely to revert to virulence. 043-93

    lmmunostimulating reconstituted influenza virosome;comprises influenza virus hemagglutinin protein and preferably a hepatitis A virus antigen, for use as vaccine Schweig. Serum Impfinst. Bern World 9219 267; 12 November 1992

    An immunostimulating reconstituted influenza virosome (IRIV) comprises: a mixture of phospholipids; essentially reconstituted functional virus envelopes; an influenza hemag- glutinin protein (HA) or a biologically active derivative capable of inducing the fusion of the IRIV with cellular membranes and of inducing lysis of the IRIV after endocytosis by antigen presenting cells, preferably macrophages or B-lymphocytes; and an antigen. Also claimed is a vaccine containing an IRIV as above, optionally in combination with a carrier and/or diluent. In a preferred IRIV, the viral envelopes are in the form of unilamellar bilayer. The antigen is derived from a pathogen e.g. a microbial pathogen, virus, bacterium or parasite, or may be an anti-idiotype antibody, toxin or toxoid, or especially hepatitis A virus (HAV) strain SB-RG XA112 (CNCM 1-1080), the VP1, VP2, VP3 or VP4 or the core protein of HAV, and is inactivated. The antigen is in the membrane of the IRIV or is inside it, or may be adsorbed to its surface. The HA derivative is preferably a HA fusion protein, and the phospholipid mixture comprises lecithin and phosphatidylethanolamine (4:1).


    Vaccine comprising non-infectious herpes virus particles; virion assembly-deficient ts 1201 mutant herpes simplex virus-1 vector for recombinant vaccine production e.g. against HIV virus Med. Res. Counc. World 9219 748; 12 November 1992

    A new virus preparation is based on herpes virus (preferably herpes simplex virus-l) particles which are virus-related, non-infectious light (L) particles of a herpes virus lacking a capsid, and free of virions. The following are also new: a vaccine based on the particles, comprising tegument surrounded by an envelope but lacking the capsid and viral DNA within the capsid, and an immunostimulant or vehicle; and L particles as above. The numerical ratio of L particles to infectious virions is at least 10 000:1. The L particles are of a conditional lethal mutant which, under conditions non-permissive for viral growth, is able to produce viral DNA and late protein, but is unable to assemble infectious virions. The mutant is preferably a temperature-sensitive ts 1201 mutant, and non-permissive

    0264-410X/93/08/0687-02 1993 Butterworth-Heinemann Ltd Vaccine, Vol. 11, Issue 6, 1993 687

  • temperature conditions are used in the latter case. The virus is preferably in inactivated form. The L particles are useful for production of vaccines free of contaminating virus, and may contain a recombinant protein or peptide, for use as vectors for recombinant vaccines, e.g. against HIV virus (claimed).


    Plasmid pMS9-2 containing the Mycobacterium tuberculosis 38 kDa antigen; expression in Escherichia coli, protein renaturation from the inclusion body and its use as a vaccine and in diagnosis of tuberculosis Ges. Biotechnol. Forsch DE 4116 249; 19 November 1992

    New hybrid plasmid pMS9-2 for expression of the Mycobact- erium tuberculosis 38 kDa antigen also contains its signal peptide, and is constructed from plasmid pJLA603. The following are also new: (1) Escherichia coil containing the plasmid; (2) the 38 kDa antigen of M. tuberculosis; and (3) the 38 kDa antigen which has been renatured from inclusion bodies by solubilizing in guanidine-HC1 (6M), in the presence of a reducing agent such as dithiothreitol, and then renatured with Sephadex chromatography e.g. Sephadex G-25 chromatography. The 38 kDa antigen is specific for M. tuberculosis, which is carried by most M. tuberculosis patients. It can therefore be used in diagnosis of tuberculosis, and for distinction from other Mycobacterium spp., and as a recombinant vaccine. In an example, a 2kb EcoRI fragment of phage lambda AA59 containing the 38 kDa gene sequence was cloned into phage M13mpl9. A 1.2kb NdeI-SphI fragment was cloned into plasmid pJLA603. The resulting plasmid was named plasmid pMS9-2 and was expressed in E. coli CAG629. The 38 kDa antigen was present in inclusion bodies at 10% total cell protein.


    Recombinant DNA encoding an analogue of Vibrio cholerae catalytic subunit; has no catalytic activity and is useful as a vaccine for preventing cholera Amgen; Univ. Southern Calif. World 9219 265; 12 November 1992

    A new, recombinant DNA molecule encodes an analogue of a catalytic subunit of cholera toxin. The analogue has reduced or no catalytic activity associated with cholera toxin reactogenicity.

    Also claimed are: (1) a genetically engineered analogue of the catalytic subunit of cholera toxin; (2) an improved anti-cholera vaccine comprising an effective amount of the analogue; (3) a pro-or eukaryotic cell (especially Escherichia coil) transformed with a DNA sequence, capable of expressing the products encoded by the DNA; (4) a Vibrio cholerae strain containing a genetically engineered toxin operon in which at least one amino acid responsible for CT reactogenicity has been altered or deleted by mutagenesis; (5) production of the cholera toxin analogue by (i) identifying at least one amino acid associated with catalytic activity, (ii) effecting site-directed mutagenesis of the toxin cistron or operon to remove or replace these residues, and (iii) expressing the mutagenized cistron or operon in a transformed organism to produce a toxoid with reduced or no catalytic activity; and (6) an isolated genetically engineered protein with a specified 240 amino aci