Glycosidase regimen for treatment of infectious disease

Abstract

In various aspects, the invention relates to immune tolerant glycosidase therapy. The invention provides methods for treating or preventing infectious disease, including chronic viral infections, and highly contagious infectious agents that present an ongoing challenge for the immune system. The compositions and treatment regimens find use with other antiviral or antimicrobial therapies, as well as in conjunction with vaccination to boost effectiveness and/or extend the duration of protective effect. In certain embodiments, the regimen described herein reduces or eliminates the need for administration of other traditional antiviral or antimicrobial therapies. In various embodiments, the invention finds use in immunocompromised patients to boost immune function.

1 . A method for treating a patient having a chronic viral infection, comprising:
 administering a non-acute regimen of an immunotolerant and immune-signaling glycosidase composition to the patient so as to treat, ameliorate, and/or manage said infection.   
     
     
         2 . The method of  claim 1 , wherein the patient is HIV positive. 
     
     
         3 . The method of  claim 2 , wherein the patient has AIDS. 
     
     
         4 . The method of any one of  claims 1  to  3 , wherein the patient is not undergoing antiviral chemotherapy, and/or the HIV is resistant to antiviral therapy. 
     
     
         5 . The method of  claim 3 , wherein the regimen is initiated after antiviral therapy to manage chronic AIDS. 
     
     
         6 . The method of  claim 3 , wherein the composition is administered with antiviral therapy to reverse disease trajectory, and optionally continued for at least six months, or at least one year, or at least two years, or at least five years to manage the infection optionally without ARV treatment. 
     
     
         7 . The method of any one of  claims 1  to  6 , wherein the patient's CD4 count at the start of said regimen is less than 500. 
     
     
         8 . The method of  claim 7 , wherein the patient's CD4 count at the start of said regimen is between 200 and 400. 
     
     
         9 . The method of  claim 7 , wherein the patient's CD4 count at the start of said regimen is less than 400, less than 350, less than 300, less than 200, less than 100, or less than 50. 
     
     
         10 . The method of any one of  claims 2  to  9 , wherein the viral load at the start of said regimen is above 10,000 per ml. 
     
     
         11 . The method of  claim 10 , wherein the viral load at the start of said regimen is at least 25,000 per ml, at least 40,000 per ml, at least 50,000 per ml, at least 75,000 per ml, at least 100,000 per ml, at least 500,000 per ml, at least 1 million per ml, or at least 5 million per ml. 
     
     
         12 . The method of  claim 1 , wherein the patient has a chronic viral infection selected from a herpes simplex virus infection, varicella zoster virus infection, hepatitis A, B, or C, adenovirus infection, or human papilloma virus infection. 
     
     
         13 . The method of claim wherein the patient has shingles. 
     
     
         14 . The method of any one of  claims 1  to  13 , wherein the glycosidase regimen comprises administration of neuraminidase. 
     
     
         15 . The method of  claim 14 , further comprising administration of one or more of galactosidase, N-acetylgalactosidase, fucosidase, glucosidase, N-acetylglucosaminidase, and mannosidase. 
     
     
         16 . A method for treating a patient having a persistent or recurrent bacterial infection, comprising, administering a regimen of glycosidase to the patient. 
     
     
         17 . The method of  claim 16 , wherein the bacterial infection is associated with pneumonia, bronchitis, sinusitis, enteritis, colitis, sepsis, or urinary tract infection. 
     
     
         18 . The method of  claim 16 , wherein the bacterial infection is a persistent or recurrent ear, eye, nose and/or throat infection. 
     
     
         19 . The method of any one of  claims 16  to  18 , wherein the bacteria is a species of  Mycobacterium, Pseudomonas, Haemophilus, Moraxella, Chlamydia, Neisseria, Streptococcus, Staphylococcus, Bordetella , or  Yersinia.    
     
     
         20 . The method of  claim 19 , wherein the bacteria is  Mycobacterium tuberculosis.    
     
     
         21 . The method of any one of  claims 16  to  20 , wherein the glycosidase regimen is administered after at least one round of antibiotic therapy has failed to ameliorate or eliminate the infection. 
     
     
         22 . The method of any one of  claims 14  to  18 , wherein the glycosidase regimen is administered alongside antibiotic therapy. 
     
     
         23 . The method of  claim 20 , wherein the antibiotic therapy is with one or more of an aminoglycoside, a carbapenum, a cephalosporin, a macrolide, a beta lactam, a quinolone, sulfonamide, or a tetracycline. 
     
     
         24 . The method of any one of  claims 16  to  23 , wherein the glycosidase regimen comprises administration of neuraminidase. 
     
     
         25 . The method of  claim 24 , further comprising administration of one or more of galactosidase, N-acetylgalactosidase, fucosidase, glucosidase, N-acetylglucosaminidase, and mannosidase. 
     
     
         26 . A method for treating a fungal or parasitic infection, comprising, administering a glycosidase regimen to a patient in need thereof. 
     
     
         27 . The method of  claim 26 , wherein the infection is candidiasis. 
     
     
         28 . The method of  claim 26 , wherein the infection is malaria or trypanosomiasis. 
     
     
         29 . The method of any one of  claims 26  to  28 , wherein the glycosidase regimen comprises administration of neuraminidase. 
     
     
         30 . The method of  claim 29 , further comprising administration of one or more of galactosidase, N-acetylgalactosidase, fucosidase, glucosidase, N-acetylgtucosaminidase, and mannosidase. 
     
     
         31 . A method for enhancing vaccination, comprising administering a regimen of an immune-signaling glycosidase to the patient, the regimen starting before, during, or after vaccination. 
     
     
         32 . The method of  claim 31 , wherein the vaccine is an adjuvant-free vaccine. 
     
     
         33 . The method of any one of  claims 1  to  32 , wherein the glycosidase is administered by a route selected from sublingual, nasal, port, subdermal, gavage, intraocular, intravenous, intramuscular, subcutaneous, transdermal, and buccal. 
     
     
         34 . The method of  claim 33 , wherein the glycosidase is administered sublingually. 
     
     
         35 . The method of any one of  claims 31  to  34 , wherein the glycosidase regimen comprises administration of neuraminidase. 
     
     
         36 . The method of  claim 35 , further comprising administration of one or more of galactosidase, N-acetylgalactosidase, fucosidase, glucosidase, N-acetylgucosaminidase, and mannosidase. 
     
     
         37 . The method of any one of  claims 1  to  36 , wherein the glycosidase is a glycosidase of biological origin, or a derivative or active moiety thereof, which maintains immunomodulating activity. 
     
     
         38 . The method of  claim 35  or  36 , wherein the glycosidase is from a biological or is synthetic. 
     
     
         39 . The method of any one of  claims 1  to  38 , wherein the glycosidase is administered on average from 2 to 6 times per day for at least one month. 
     
     
         40 . The method of  claim 39 , wherein the glycosidase is administered on average from 2 to 6 times per day for at least two months, at least four months, or at least six months. 
     
     
         41 . The method of  claim 39 , wherein the patient is subsequently treated chronically with about one dose per day, for at least six months, or at least one year, or at least two years, or at least five years, or more. 
     
     
         42 . A drug applicator for administration of a glycosidase composition, the applicator comprising at least 100 doses of the neuraminidase composition. 
     
     
         43 . The drug applicator of  claim 42 , wherein the applicator is for sublingual, nasal, transdermal, time release sub-dermal, intraocular, gavage, port, subcutaneous, oral, or buccal delivery. 
     
     
         44 . The drug applicator of  claim 42  wherein the applicator is for sublingual delivery. 
     
     
         45 . The drug applicator of any one of  claims 42  to  44 , wherein the applicator dispenses doses in a manner that maintains aseptic conditions of the remaining doses. 
     
     
         46 . The drug applicator of  claim 45 , wherein the applicator delivers a dose in from 50 to 100 μl. 
     
     
         47 . The drug applicator of any one of  claims 42  to  46 , wherein the glycosidase comprises neuraminidase. 
     
     
         48 . The drug applicator of any one of  claims 42  to  46 , wherein the glycosidase comprises at least two of neuraminidase, galactosidase, N-acetylgalactosidase, fucosidase, glucosidase, N-acetylglucosaminidase, and mannosidase.