Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Patent
1995-04-19
1999-08-17
Campell, Bruce R.
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
514 44, 536 231, 4353201, 435 691, 435455, A61K 4800
Patent
active
059390646
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with a vaccine protective against Bordetella bronchiseptica infection in dogs, with polypeptides characteristic of B. bronchiseptica and with the preparation thereof using rec. DNA-technology.
The genus Bordetella is comprised of four species: Bordetella pertussis (B. pertussis), Bordetella parapertussis(B. parapertussis), Bordetella bronchiseptica (B. bronchiseptica) and Bordetella avium (B. avium). Bordetella are small gram-negative coccobacilli, obligate aerobic, often bipolar stained, and cytochrome oxidase positive. Colonies on Bordet-Gengou medium are surrounded by a zone of hemolysis except for B. avium.
All species of Bordetella cause very similar disease with respect to adherence, proliferation, clinical symptoms, and histopathology. Infants of man and animals are most susceptible to infection with Bordetella. Here the disease is most severe and mortality is the highest.
B. bronchiseptica is primarily a pathogen of laboratory, domestic and wild animals and only occasionally man. Rabbits, guinea pigs, rats, non-human primates, dogs, swine, cats, horses and foxes are often infected in epidemic. B. bronchiseptica most notably causes kennel cough in dogs and atrophic rhinitis in piglets. In dogs the infectious process is largely limited to the tracheobronchial tree and is characterized by proliferation on the tracheal epithelium, after adherence to the cilia. The most severe symptoms of the disease are excessive tracheal mucus accumulation, vomiting, pulmonary lesions and weight loss. Dogs have a dry, harsh hacking cough. Infection of piglets with B. bronchiseptica is characterized by turbinate atrophy, snout deformity, pneumonia and reduced weight gain. Although it seemed clearly established that B. bronchiseptica was the responsible agent of atrophic rhinitis, considerable evidence now indicates that Pasteurella multocida is the major phathogen with B. bronchiseptica possibly playing an inducing or opportunistic role. The reported carrier states, without clinical signs, are high for dogs, swine and rabbits.
Several virulence factors have been identified in Bordetellae. These include: pertussis toxin, filamentous hemagglutinin, fimbriae, adenylate cyclase, dermonecrotic toxin, tracheal toxin, and hemolysin. These virulence factors are not expressed in all species, for example the gene encoding pertussis toxin in B. pertussis is present as a silent gene of the chromosome of B. parapertussis and B. bronchiseptica. Besides these virulence factors there are probably more, yet unidentified, factors involved in pathogenicity of the bacteria.
Bordetella infections start at the ciliated cells of the respiratory tract. Bacterial adherence is a prerequisite for the initiation of infection since otherwise the flushing action of the cilia removes the bacteria together with other particles from the trachea. Adherence of Bordetella to ciliated cells is mediated by serologically different fimbriae and the filamentous hemagglutinin (FHA) (FHA is not found in B. avium however). Fimbriae are hairlike structures, composed of identical subunit proteins, extending from the bacterial cell surface. The FHA is a surface-associated protein also excreted into the extracellular environment and able to agglutinate a variety of erythrocytes. Both fimbriae and FHA expression is regulated by the bvg-locus although expression of fimbrial subunit genes, in B. pertussis, is also influenced by the length of a stretch of 13-15 cytosine residues in front of the fimbrial subunit genes. All virulent Bordetellae express adherence factors on their surface whereas nonvirulent strains do not. Since these adhesins are essential for the initiation of the disease, these are attractive vaccine components.
The purpose of the present invention is to provide a recombinant-DNA vaccine against B. bronchiseptica infection. Research has been focused on adhesion factors since prevention of adhesion, as a result of an immune response directed against adhesion factors, will prevent an infection. In B. bronchiseptica sever
REFERENCES:
patent: 4920048 (1990-04-01), Diderichsen
Immunology, vol. 78, No. 6, pp. 3824-3828, Jun. 1981, Proc. Natl. Acad. Sci., USA, "Prediction of protein antigenic determinants from amino acid sequences", Thomas P. Hopp et al.
Advances in Immunology, 47, pp. 45-148, Peter Y. Chou et al., "Prediction of the Secondary Structure of Protein from their Amino Acid Sequence".
Naturwissenschaften 72 (1985), P.A. Karplus, et al., "Prediction of Chain Flexibility in Proteins: A Tool for the Selection of Peptide Antigens".
Biophys. J., Biophysical Society, vol. 26, Jun. 1979, pp. 367-384, Peter Y. Chou et al., "Prediction of .beta.-Turns".
CABIOS, vol. 4, No. 3, 1988, pp. 357-365, O. Gascuel et al., "A simple method for predicting the secondary structure of globular proteins: implications and accuracy".
Nucleic Acids Research, vol. 12, No. 1, 1984, pp. 243-255, Jiri Novotny et al., "A program for prediction of protein secondary structure from nucleotide sequence data: application to histocompatibility antigens".
Proc. Natl. Acad. Sci., vol. 81, Jul. 1984, pp. 3998-4002, H. Mario Geysen et al., "Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid".
The EMBO Journal, vol. 3, No. 6, 1984, pp. 1429-1434, Keith K. Stanley et al., "Construction of a new family of high efficiency bacterial expression vectors: identification of cDNA clones coding for human liver proteins".
The Journal of Immunology, vol. 143, No. 8, Oct. 15, 1989, pp. 2692-2698, Johannes G. Kusters et al., "Analysis of an Immunodominant Region of Infectious Bronchitis Virus".
Microbial Pathogenesis, vol. 2, 1987, pp. 473-484, Frits R. Mooi et al., "Characterization of fimbrial subunits from Bordetella species".
Abstracts of General Meeting of Am. Soc. Microbiol., vol. 92, p. 193, Eugene H. Burns, Jr., "Comparison of Fimbrial Serotype 2 Subunit Antigen Expression Levels in Bordetella bronchiseptica Strains".
Molecular Microbiology, vol. 2, No. 4, 1988, pp. 539-543, P. Pendroni et al., "Cloning of a novel pilin-like gene from Bordetella pertussis: homology to the fim2 gene".
Nucleic Acids Research, vol. 17, No. 19, 1989, p. 8007, Johannes G. Kusters et al., "Improvements of the cloning linker of the bacterial expression vector pEX".
Molecular Microbiology, vol. 1, No. 2, 1987, pp. 203-209, I. Livey et al., "Cloning and nucleotide sequence analysis of the serotype 2 fimbrial subunit gene of Bordetella pertussis".
Ngo et al., The Protein Folding Problem and Tertiary Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 492-495.
Makela et al. (1996) Vaccine, vol. 14, No. 7: 719-732.
Robert Whalen (1996) Emerging Infectious Diseases, vol. 2, No. 3:168-175.
Etlinger (1992) Immunology Today, vol. 13, No. 2: 52-55.
Glick et al. (1994) Molecular Biotechnology, ASM Press:214.
Burns et al. (1993) J. Clin. Microb., vol. 31, No. 7: 1838-1844.
Gaastra Willem
Savelkoul Paul
American Cyanamid Company
Campell Bruce R.
Nguyen Dave Trong
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