Use of coxiella bacteria to treat autoimmune disease

Details Use of coxiella bacteria to treat autoimmune disease Use of coxiella bacteria to treat autoimmune disease

1999-03-05

2004-09-14

Devi, S. (Department: 1645)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Bacterium or component thereof or substance produced by said...

C424S236100, C424S282100, C424S278100, C424S093400, C424S810000, C514S866000, C514S002600

Reexamination Certificate

active

06790450

ABSTRACT:

TECHNICAL FIELD
The present invention relates generally to a method for ameliorating the adverse effects of autoimmune conditions and to therapeutic conditions useful for same. More particularly, the present invention provides a method for the prophylaxis and/or treatment of insulin-dependent diabetes mellitus (IDDM) by preventing, inhibiting, delaying onset of, or otherwise ameliorating the effects of the disease. The present invention further provides a method for the prophylaxis and/or treatment of pancreatic beta cell destruction in islet tissue transplanted into recipients. The present invention also provides therapeutic compositions useful in the prophylaxis and/or treatment of IDDM and pancreatic beta cell destruction.
BACKGROUND OF THE INVENTION
IDDM is a debilitating, chronic cell mediated autoimmune disease characterised by lymphocytic infiltration of the pancreatic islets and lymphocyte mediated destruction of insulin-producing beta-cells (Bach 1994, Honeymoon and Harrison, 1993) and is defined by the presence of hyperglycemia. Type 1 diabetes, or IDDM, occurs where an individual's own immune system destroys the cells responsible for insulin production; the beta cells residing in the islets of Langerhans of the pancreas. IDDM in humans, in the non-obese diabetic mouse (NOD mouse [Makino et al, 1980; Kanazawa et al, 1984]) and in the BB rat is an autoimmune disease associated with the development of auto-antibodies reactive to islet-associated antigens (Atkinson et al., 1986). Susceptibility to the development of disease both in humans and in non-human animals is under genetic control. Genes of the major histocompatibility complex (MHC), specifically those found in the class II MHC region, which control structures involved in the presentation of antigen to the cellular components of the immune system are to a large extent responsible for the disease-prone status (Davis et al., 1989).
In animal models, a single immunostimulation with live, infectious BCG (
Mycobacterium bovis
; Bacille Calmette-Guérin) vaccination (Yagi et al., 1991) or powerful immuno-adjuvants based on heat-killed Mycobacterium tuberculosis (or
Mycobacterium butyricum
) either early or late in the disease process, can largely suppress the development or progression of disease respectively (reviewed in Bach, 1994). Freund's Complete Adjuvant (FCA) [often referred to as complete Freund's adjuvant or CFA], which consists of a suspension of heat-killed M. tuberculosis (or
M. butyricum
) in mineral oil together with a surfactant is considered to be a particularly powerful immunological adjuvant. Immunostimulation with a single injection of FCA has been shown to substantially protect both NOD mice (Sadelain et al., 1990a; McInerney et al., 1991) and BB rats (Sadelain et al., 1990b) from developing diabetes.
Immuno-adjuvants such as bacterial lipopolysaccharide (LPS) or muramyl dipeptide (MDP) which are not based upon either live or heat-killed Mycobacterium sp. are not effective in preventing diabetes.
Another biological response modifier, OK-432, prepared from streptococci, when administered to NOD mice, has been shown to prevent the onset of diabetes until mice reach 24 weeks of age (Toyota et al., 1986); no information exists showing whether or not these animals remain free of diabetes once the therapy is discontinued. It has also been shown that the immunomodulating drug quinoline-3-carboxamide (Linomide) when given continuously in the drinking water to NOD mice, starting at a young age (5 weeks), will block the onset of diabetes until the mice are at least 40 weeks old (Gross et al., 1994). However, this agent is not as effective when therapy is started on mice which are 16 weeks old; in this case the cumulative incidence of diabetes is 28% by the time the mice are 42 weeks old even though the drug is given on a continuous basis (Gross et al., 1994).
FCA appears to induce cell-mediated protection against development of diabetes. It has, for example, been shown that spleen cells taken from NOD mice, which had been treated with FCA, were capable of suppressing the response of co-cultured control syngeneic spleen cells to mitogens (Sadelain et al., 1990a; McInerney et al., 1991). When spleen cells are taken from BCG vaccinated NOD mice and passaged into naive NOD mice, the latter are protected from developing diabetes (Harada et al., 1990; Yagi et al., 1991). The same effect has been observed in FCA-treated BB rats (Qin et al., 1992). It should be noted that others have found FCA to be less effective than BCG in transferring protection in this manner (Qin et al., 1993; Ulaeto et al., 1992).
Recurrence of disease in grafted tissue is a major factor which interferes with the transplantation of pancreatic islets into spontaneously diabetic NOD mice. Currently it is not possible to successfully transplant islets into animus that have developed disease hi spontaneously without recourse to extensive immunosuppression (Wang et al., 1991). Recurrence of disease can, however, be blocked in spontaneously diabetic NOD mice if they are treated with FCA (Wang et al., 1992; Lakey et al., 1992) or BCG (Lakey et al., 1994) prior to transplantation.
Immunostimulation of NOD mice by either BCG or FCA does not totally block the autoimmune response, instead the response is converted from a destructive into a non-destructive form of auto-immunity (Shehadeh et al., 1993). Thus, functionally these agents do not prevent or reverse autoimmunity directed against islet tissue, although they do prevent development of insulin-dependent diabetes.
It would appear, therefore, that deviation of the immune response away from destructive autoimmunity by immunostimulation could offer a benign approach to the prevention of diabetes and the development of more effective means for the transplantation of islets in the case of existing disease.
However, neither FCA nor BCG is an ideal therapeutic agent for preventing the development, of IDDM. Despite the fact that FCA is a very powerful immuno-adjuvant, it has not found wide-spread use outside the laboratory because of the adverse tissue reaction (severe ulceration) it provokes in mammals. In most countries, FCA is banned from veterinary use and, of course, it cannot be used in humans. BCG is an infectious agent which cannot be given to certain individuals, especially those who are immunosuppressed.
SUMMARY OF THE INVENTION
In work leading to the present invention, the inventors sought to develop agents capable of blocking the development of IDDM in humans which are sufficiently benign for general use and most effective in terms of deviating the immune response away from destructive autoimmunity.
Accordingly, one aspect of the present invention contemplates a method for preventing, inhibiting, delaying onset of or otherwise ameliorating the effects of an autoimmune disease in a mammal, said method comprising administering to said mammal an autoimmune-preventing effective amount of a species of Coxiella or one or more antigenic components therefrom or analogous or homologous components thereof.
Another aspect of the present invention provides a method for prolonging survival of islet tissue transplanted into a mammal, said method comprising administering into said mammal an effective amount of a species of Coxiella or one or more antigenic components therefrom or analogous or homologous components thereof.
Still a further aspect of the present invention is directed to a therapeutic composition for use in preventing, inhibiting, delaying onset of or otherwise ameliorating the effects of an autoimmune disease in a mammal said composition comprising a species of Coxiella or one or more antigenic components therefrom or analogous or homologous components thereof and one or more pharmaceutically acceptable carriers and/or diluents.
Yet still another aspect of the present invention relates to the use of a species of Coxiella or one or more antigenic components therefrom or analogous or homologous components thereof in the manufacture of a medicament for the treat

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