Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Patent
1998-09-17
2000-02-22
Minnifield, Nita
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
4242411, 4241841, 4242341, 4242361, 4242781, 424422, 424489, 536 41, 536 5, 536 63, A61K 39108, A61K 3900, A61K 3938, A61K 3902, A61K 4500
Patent
active
060277327
DESCRIPTION:
BRIEF SUMMARY
The invention involves lipid-containing particles, chosen from iscoms and iscom matrices, which contain one (several) hydrophobic receptor component(s) which bind to antigens from microorganisms such as bacteria, virus, or parts thereof, i e the receptor-binding parts, such as toxins or surface proteins.
Furthermore, the invention involves procedures for producing such lipid-containing particles and the human medical, veterinary medical, or other pharmacological preventive and curative use, such as immunotherapeutic, of these particles. The invention involves in particular iscoms and iscom matrices whose surfaces have been prepared with bacterial toxin fragments such as the cholera toxin's B subunit (CTB).
THE BACKGROUND OF THE INVENTION
Lipid-containing structures in the form of micelles, liposomes and other visicles, iscoms (immune-stimulating complex/particles), iscom matrices, etc. have been reported as effective carriers of pharmacologically and/or immunologically active substances or molecule complexes. See for example WO-A1-90/03184 (Morein et. al., Clin. Immunother. Review, 1995; Kersten et. al., Iscom--Liposome Review, 1995). In many cases, immunization of laboratory animals with such lipid-containing structures, in which various antigens have been incorporated, have been shown to give rise to an increased immune response to the referred antigens as compared to the immune response obtained after immunization using a corresponding antigen in a free form.
Iscom and iscom matrices are documented as effective carriers of antigens and adjuvant molecules to enhance the immunogenicity of small and large molecules (antigens), i e to make them strongly immunogenic both when they are applied parenterally and locally, (topically) on mucous surfaces. The iscom has unique properties being effective after mucosal intranasal adminstration. It is well-documented (Morein et. al., Clin. Immunother. 3, 1995, 461-475) that both iscoms with incorporated antigens (usually protein) and iscoms as carriers, for example small antigens such as oligopeptides or as exemplified by biotin, effectively evoke immune response to these large or small molecules.
Iscom matrices (and iscom) have well-documented, built-in, adjuvant activity that potentiates antibody-mediated as well as cell-mediated immune responses to the co-administered antigens. Iscom evokes cell-mediated immune response under both Class I and Class II restriction.
Cholera is the most serious of all the diarrhea diseases and is caused by the Vibrio cholera bacteria in group 1. These bacteria colonize in the small intenstine of human beings and secrete an exotoxin protein known as the cholera toxin. This toxin binds to and is absorbed by cells in the mucous membranes and causes an intensive secretion of electrolytes and water from the cells, which leads to the grave cases of diarrhea, dehydration, and metabolic acidosis which characterize cholera.
Similar diseases can be caused by so-called "enterotoxic" (ET) cholibacteria, but the symptoms are usually milder. Such bacteria often cause diarrhea in young individuals among humans and practically all kinds of animals, including pigs and cattle. These diarrheas, which can give rise to great economic losses for the livestock industry, are caused partly by a heat-labile toxin (LT) similar to the cholera toxin (CT). These toxins are so similar that they bind to the same receptors.
The structures of CT and LT are well defined in regards to structure and function. They are oligomeric proteins consisting of one part that binds to the cholera toxin receptor, namely the B part, which in turn consists of five subunits which each have an approximate mole weight of 11,600 and form a pentamer ring. The A subunit is a proteolytic split polypeptide with a molecular weight of approximately 28,000, consisting of two disulfid-conjugated fragments. The larger A1 fragment contains toxin-enzyme activity, while the smaller A2 fragment joins the A1 fragment with the B5 ring. CT binds with high affinity to a class of receptors that exist on
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Bengtsson Karin Lovgren
Ekstrom Jill
Morein Bror
Baskar Padma
Minnifield Nita
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