Anti-Viral Treatment With Pertussis Toxin B Oligomer

Abstract

There is disclosed a method for anti-viral therapy, and for decreasing infectivity of viruses that use the chemokine CCR5 receptor as a co-receptor by treatment with the B. pertussis toxin (PTX) B oligomer, wherein the PTX B oligomer is composed of from two to ten subunits of PTX B oligomer selected from the group consisting of S2, S3, S4, S5, and combinations thereof.

We claim:  
     
         1 . A method for treating viral infections, comprising administering an effective amount of  B. pertussis  toxin (PTX) B oligomer to a patient having a viral infection, wherein the PTX B oligomer comprises from two to ten subunits of PTX selected from the group consisting of S2, S3, S4, S5, and combinations thereof, and wherein the viral infection is inhibited by a mechanism selected from the group consisting of inhibition of viral entry into the cell, inhibition of post-entry replication, inhibition of co-capping of a viral receptor or co-receptor, desensitization of a viral receptor or co-receptor, modulation of protein kinase C (PKC) activity, and combinations thereof.  
     
     
         2 . The method of  claim 1  wherein the mechanism of inhibition of the viral infection is inhibition of viral entry into the cell.  
     
     
         3 . The method of  claim 2  wherein the dose of PTX B oligomer administered each day is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         4 . The method of  claim 2  wherein the viral infection is caused by HIV.  
     
     
         5 . The method of  claim 2  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, 1S2-1S3-2S4, and 1S2-1S4-1S3-1S4-1S5.  
     
     
         6 . The method of  claim 2  wherein viral entry is mediated by the chemokine receptor CCR5.  
     
     
         7 . The method of  claim 1  wherein the mechanism of inhibition of the viral infection is inhibition of co-capping of a viral receptor or co-receptor.  
     
     
         8 . The method of  claim 1  wherein the mechanism of inhibition of the viral infection is inhibition of post-entry replication.  
     
     
         9 . The method of  claim 7  wherein the dose of PTX B oligomer administered each day is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         10 . The method of  claim 7  wherein the viral infection is caused by HIV.  
     
     
         11 . The method of  claim 7  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         12 . The method of  claim 7  wherein co-capping involves the chemokine receptor CCR5.  
     
     
         13 . The method of  claim 1  wherein the mechanism of inhibition of the viral infection is desensitization of a viral receptor or co-receptor.  
     
     
         14 . The method of  claim 13  wherein the dose of PTX B oligomer administered each day is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         15 . The method of  claim 13  wherein the viral infection is caused by HIV.  
     
     
         16 . The method of  claim 13  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         17 . The method of  claim 13  wherein the chemokine receptor CCR5 is desensitized.  
     
     
         18 . The method of  claim 1  wherein the mechanism of inhibition of the viral infection is modulation of protein kinase C (PKC) activity.  
     
     
         19 . The method of  claim 18  wherein the dose of PTX B oligomer administered each day is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         20 . The method of  claim 18  wherein the viral infection is caused by HIV.  
     
     
         21 . The method of  claim 18  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         22 . The method of  claim 18  wherein the chemokine receptor CCR5 is desensitized by modulation of protein kinase C (PKC) activity.  
     
     
         23 . A method for decreasing the infectivity of a cell or susceptibility of a cell to retroviral infection, wherein the cell expresses a CCR5 chemokine receptor, and wherein a virus uses the CCR5 chemokine receptor as a co-receptor, comprising contacting the cell with an amount of  B. pertussis  toxin (PTX) B oligomer sufficient to induce an antiviral mechanism selected from the group consisting of inhibition of viral entry into the cell, inhibition of post-entry replication, inhibition of co-capping of a viral receptor or co-receptor, desensitization of a viral receptor or co-receptor, modulation of protein kinase C (PKC) activity, and combinations thereof.  
     
     
         24 . A method for treating a CCR5 receptor-related physiological or pathological condition, comprising administering to a patient having the CCR5 receptor-related physiological or pathological condition, an amount of  B. pertussis  (PTX) B oligomer sufficient to desensitize the CCR5 receptor, wherein the PTX B oligomer is composed of from two to ten subunits of PTX selected from the group consisting of S2, S3, S4, S5, and combinations thereof.  
     
     
         25 . The method of  claim 24 , wherein the CCR5 receptor-related physiological or pathological condition is selected from the group consisting of progressive neurological disorders, HTLV-associated myelopathy, multiple sclerosis, inflammation, and infection.  
     
     
         26 . The method of  claim 24  wherein the dose of PTX B oligomer administered each day is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         27 . A vaccine formulation for vaccinating against opportunistic infections from non-HIV pathogens in HIV-infected individuals, consisting essentially of an HIV-suppressing formulation of  B. pertussis  toxin (PTX) B oligomer (PTX B oligomer), an antigenic component specific for the non-HIV pathogen, with the proviso that the non-HIV pathogen is not influenza, and a vaccine-acceptable carrier.  
     
     
         28 . The vaccine formulation of  claim 27  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         29 . The vaccine formulation of  claim 27  wherein the pathogen is selected from the group consisting of Pneumocistis, Candida, CMV (Cytomegalovirus), Hepatitis virus (A, B and C), Pneumococcus,  Mycobacterium tuberculosis, Mycobacterium aviium,  Cryptosporidium, and Aspergillis.  
     
     
         30 . The vaccine formulation of  claim 27  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         31 . A method for vaccinating against opportunistic infections from non-HIV pathogens in HIV-infected individuals, comprising administering an HIV-suppressing formulation of  B. pertussis  toxin (PTX) B oligomer (PTX B oligomer) and an antigenic component specific for the non-HIV pathogen.  
     
     
         32 . The method of  claim 31  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         33 . The method of  claim 31  wherein the pathogen is of bacterial, viral, fungal, parasitic, or mycobacterial origin.  
     
     
         34 . The method of  claim 33  wherein the pathogen is selected from the group consisting of Pneumocistis, Candida, CMV (Cytomegalovirus), Hepatitis virus (A, B and C), Pneumococcus,  Mycobacterium tuberculosis, Mycobacterium aviium,  Cryptosporidium, and Aspergillis.  
     
     
         35 . The method of  claim 31  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         36 . A method for vaccinating to protect an individual against HIV infection in an individual not infected with HIV comprising administering a vaccine composition comprising  B. pertussis  toxin (PTX) B oligomer (PTX B oligomer) and an antigenic component specific for HIV.  
     
     
         37 . The method of  claim 36  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         38 . An HIV preventive vaccine formulation consisting essentially of  B. pertussis  toxin B oligomer (PTX B oligomer), an antigenic component specific for HIV, and a vaccine-acceptable carrier.  
     
     
         39 . The HIV preventive vaccine formulation of  claim 38 , wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         40 . The HIV preventive vaccine formulation of  claim 38 , wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         41 . A method for treating HIV infection, comprising administering  B. pertussis  toxin B oligomer (PTX B oligomer) in combination with an anti-HIV agent, wherein the HIV agent is selected from the group consisting of protease inhibitors, reverse transcriptase inhibitors, nuclear localization importation inhibitors, and combinations thereof.  
     
     
         42 . The method for treating HIV infection of  claim 41  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         43 . The method for treating HIV infection of  claim 41  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         44 . A method for preventing HIV infection in an individual recently having transmissable contact with an HIV-infected individual, comprising administering  B. pertussis  toxin (PTX) B oligomer (PTX B oligomer) in combination with an agent selected from the group consisting a nuclear localization importation inhibitor, reverse transcriptase inhibitors, protease inhibitors, and combinations thereof.  
     
     
         45 . The method for preventing HIV infection in an individual recently having transmissable contact with an HIV infected individual of  claim 44  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         46 . The method for preventing HIV infection in an individual recently having transmissable contact with an HIV infected individual of  claim 44  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.  
     
     
         47 . A pharmaceutical composition for treating viral infections consisting essentially of PTX B oligomer and a pharmaceutically acceptable carrier.  
     
     
         48 . The pharmaceutical composition of  claim 47  wherein the dose of PTX B oligomer administered is from about 0.01 mg/kg to about 500 mg/kg.  
     
     
         49 . The pharmaceutical composition of  claim 47  wherein the PTX B oligomer is selected from the group consisting of 1S2-1S4, 1S3-1S4, 1S2-1S3-2S4-1S5, and 1S2-1S3-2S4.