Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor
Patent
1993-03-16
1996-03-19
Mosher, Mary E.
Chemistry: molecular biology and microbiology
Micro-organism, per se ; compositions thereof; proces of...
Bacteria or actinomycetales; media therefor
4241901, 4241921, 435 693, 4352402, 43525411, 4353201, 536 234, 536 237, C12N 1531, C12N 1562, C12N 510, A61K 3908
Patent
active
055003664
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to isolated or synthetic sequences of or derived from TraT (a protein molecule isolated from the outer-membrane of certain strains of Escherichia coli) which function as T-cell epitopes. Such sequences can be employed in the preparation of vaccines which involve the use of carrier peptides to enhance antibody production to an immunogen and/or stimulate strong cell-mediated immunity to the immunogen whilst avoiding the use of larger carrier protein molecules.
BACKGROUND ART
The generation of an immune response against a pathogen (bacterial, viral or parasite) depends, in the first instance, on the delivery of the appropriate stimulus to the immune system of the host. The pathogen or infectious agent presents the host with a number of immune-stimulating compounds or antigens which are usually large molecules such as proteins, polysaccharides or glycoproteins. These antigens may provoke one or more different types of reaction from the host in an effort to destroy or eliminate the invading organism. Accordingly, the antigen may stimulate T-cells which provide cell-mediated immunity and/or an antigen may stimulate B cells to initiate the synthesis and secretion of antibody (humoral immunity). The development and maintenance of the individual's protective immune response to a foreign antigen is usually dependent on achieving a critical level of stimulation of both cell-mediated and humoral immunity.
In the generation of a protective immune response, a certain type of T-cell, a helper T-cell is frequently required to assist the B-cell to grow and secrete soluble antibody. These helper T-cells also interact with and recognize antigens on the surface of antigen-presenting cells such as macrophages and, by releasing soluble factors (cytokines), mediate activation and differentiation of B-cells.
Certain small molecules termed haptens, of which short peptides are an example, are usually poorly immunogenic while larger molecules such as proteins and some polysaccharides are usually immunogenic in that they elicit a satisfactory protective response. To obviate the problems of inducing immunity to poorly immunogenic molecules, attempts have been made to enhance their immunogenicity by binding them to "carrier" molecules. These carriers, which are usually immunogenic proteins, function by stimulating the T-cell co-operative effect that occurs with naturally immunogenic molecules. That is to say, a poorly immunogenic antigen, bound to a carrier, will elicit T-cell help in antibody production. By engaging the T-cells with carrier determinants, B-cells will begin antibody production not only to the carrier itself, but also to the bound antigenic determinant.
Although it is widely accepted that the carrier principle is an effective method of improving the efficacy of vaccines, the number of proteins which are ethically accepted for use as potential carrier proteins for human use is relatively limited. These include tetanus toxoid and diphtheria toxoid. The limited number of available carrier proteins means that a large number of vaccine products will employ one of these proteins and multiple immunizations with products conjugated to these carriers increases the possibility that undesirable reactions to these carriers will occur. Also, these carriers have been chosen in the first instance, not for their immunostimulatory characteristics, but rather because they were already registered for human use. It is clear, therefore, that there is a need for an alternative carrier to those currently used in conjugate vaccines which will obviate the immunological problems associated with these vaccines and yet retain the same immunogenicity as the vaccines presently in use or improve on it.
During the past decade it has become clear that certain fragments of proteins, rather than the entire protein molecule, are preferentially recognized by T-cells in association with an appropriate self (Class I or Class II) antigen. These fragments are known as T-cell epitopes and their co-recognition (i
REFERENCES:
patent: 5403586 (1995-04-01), Russell-Jones et al.
Jalajakumari et al. J. Mol. Biol. 198:1-11 1987.
Finlay et al. J. of Bacteriology 166(3): 713-721 (1986).
Adorini, L. et al., "Mechanisms Influencing the Immunodominance of T-cell determinants".
The Journal of Experimental Medicine, vol. 168; pp. 2091-2104. (Dec. 1988).
Avrameas, S. et al., "Coupling of Enzymes to Antibodies and Antigens", Scand. J. Immunol., vol. 8, (Suppl. 7) pp. 7-23 (1978).
Buus, S. et al., "A Group-specific Inhibitor of Lysosomal Cysteine Proteinases Selectively Inhibits Both Proteolytic Degradation and Presentation of the Dinitrophenyl-poly-L-lysine by Guinea Pig Accessory Cells to T-cells", The Journal of Immunology, vol. 136, No. 2, pp. 452-458, (Jan. 1986).
Chanh, T. C. et al., "Synthetic Peptides Homologous to HIV Transmembrane Glycoprotein Suppress Normal Human Lymphocyte Blastogenic Response", Cellular Immunol. 111, pp. 77-86 (1988).
Chouaib, S. et al., "Generation of Lymphokine-activated Killer Cells: Synergy Between Tumor Necrosis Factor and Interleukin 2", Proc. Natl. Acad. Sci. USA vol. 85, pp. 6875-6879 (Sep. 1988).
Delisi, C. et al., "T-cell Antigenic Sites Tend to be Amphipathic Structures", Proc. Natl. Acad. Sci. USA, vol. 82, pp. 7048-7052 (Oct. 1985).
Tsai, C. M. et al., "A Sensitive Silver Stain for Detecting Lipopolysaccharides in Polyacrylamide Gels", Analytical Biochemistry 119, pp. 115-119 (1982).
Webster, C. J., "Principles of a Quantitative Assay for Bacterial Endotoxins in Blood that Uses Limulus Lysate and a Chromogenic Substrate", Journal of Clinical Microbiology, vol. 12, pp. 644-650 (1980).
Bolivar, F. et al., "Construction and Characterization of New Cloning Vehicles, II. A Multipurpose Cloning System", Gene 2, pp. 95-113. (1977).
Ogata, R. T. et al., "Nucleotide Sequence Analysis of the Complement Resistance Gene from Plasmid R100", Journal of Bacteriology, vol. 151, No. 2, pp. 819-827 (1982).
Perumal, N. B. et al., "The Product of the F Sex Factor traT Surface Exclusion Gene is a Lipoprotein", The Journal of Biological Chemistry, vol. 259, No. 9, pp. 5357-5360 (1984).
Perumal, N. B. et al., "Biochemical Characterization of the F Sex Factor traT surface Gene Product", Dissertation Abstracts International, vol. 46, No. 5, p. 160 (1985).
Sukupolvi, S. et al., "Amino Acid Alterations in a Hydrophobic Region of the TraT Portein of R6-5 Increase the Outer Membrane Permeability of Enteric Bacteria", Mol. Gen. Genet. 210, pp. 178-180 (1987).
Sukupolvi, S. et al., "Characterization of the TraT Gene and Mutants that Increase Outer Membrane Permeability from the Salmonella typhimurium virulence plasmid", Mol. Microbiol. 4(1), pp. 49-57 (1990).
Taylor, I. M. et al. "The TraT Lipoprotein as a Vehicle for the Transport of Foreign Antigenic Determinanats to the Cell Surface of Escherichia coli K12: Structure-function Relationships in the TraT Protein", Mol. Microbiol. 4(8), pp. 1259-1268 (1990).
Sukupolvi, S. et al., "TraT Lipoprotein, a Plasmid-specified Mediator of Interactions Between Gram-Negative Bacteria and their Environment", Microbiological Reviews, vol. 54, No. 4, pp. 331-334 (1990).
Croft, S. et al., "TraT: A Powerful Carrier Molecule for the Stimulation of Immune Responses to Protein and Peptide Antigens", The Journal of Immunology, vol. 146, No. 3, pp. 793-798 (1991).
Geczy Andrew F.
Russell-Jones Gregory J.
Biotech Australia Pty. Ltd.
Caputa Anthony
Mosher Mary E.
LandOfFree
Polynucleotide encoding T-cell epitopes of the protein TraT does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polynucleotide encoding T-cell epitopes of the protein TraT, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polynucleotide encoding T-cell epitopes of the protein TraT will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1959028