Immunokine composition and method

Abstract

A composition and method for preventing HIV infection of mammalian cells. One aspect of the invention relates to an anti-immunodeficiency virus immunokine capable of binding to a cellular protein in a manner that prevents HIV infection of that cell. The compositions can include either an active bioactive polypeptide, such as native cobratoxin, and/or an inactivated bioactive polypeptide, such as cobratoxin in which one or more of the native disulfide bridges have been prevented from forming. The term “immunokine” is used to refer to an inactivated bioactive polypeptide, whether inactivated by chemical, genetic, and/or synthetic means as described herein, with the proviso that a corresponding active bioactive polypeptides can be included where applicable (e.g., for in vitro use).

1 . A composition according to  claim 9  wherein the inactive bioactive polypeptide comprises an anti-immunodeficiency virus immunokine capable of binding to a cellular protein in a manner that reduces HIV infection of the cell, wherein
 a) the immunodeficiency virus is selected from the group consisting of HIV-1, HIV-2 and SIV, or   b) the protein to which the immunokine of the invention binds is selected from the group consisting of CD4, CXCR4 and CCR5.   
     
     
         2 .- 3 . (canceled) 
     
     
         4 . A composition according to  claim 1  wherein the inactivated bioactive polypeptide comprises a toxin selected from neurotoxins affecting the presynaptic neurojunction, toxins affecting postsynaptic neurojunction, and toxins affecting ion channels. 
     
     
         5 . A composition according to  claim 4  wherein the toxin comprises α-cobratoxin. 
     
     
         6 . A composition according to  claim 1  wherein the immunokine is adapted to bind one or more of a chemokine receptor protein, and a cellular cofactor for a cellular HIV receptor protein. 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . A composition comprising an inactivated bioactive polypeptide comprising a substantially native toxin structure wherein one or more of the disulfide bridges are substantially lacking as the result of ozonation performed in a stoichiometric manner. 
     
     
         10 . A composition according to  claim 9  wherein the inactivated bioactive polypeptide comprises inactivated alpha-cobratoxin in which the disulfide bridges are substantially lacking by stoichiometric ozonation of native alpha-cobratoxin. 
     
     
         11 .- 15 . (canceled) 
     
     
         16 . A composition comprising an anti-immunodeficiency virus immunokine capable of binding to a cellular protein in a manner that reduces HIV infection of the cell, wherein the immunodeficiency virus is selected from the group consisting of HIV-1, HIV-2 and SIV and the immunokine comprises an inactivated bioactive polypeptide, wherein the protein to which the immunokine of the invention binds is selected from the group consisting of CD4, CXCR4 and CCR5, and wherein the immunokine provides a substantially native toxin structure wherein one or more of the disulfide bridges are lacking by a method selected from the ozonation of native toxin, genetic engineering, and protein synthesis. 
     
     
         17 . A composition according to  claim 16  wherein the inactivated bioactive polypeptide comprises a toxin selected from neurotoxins affecting the presynaptic neurojunction, toxins affecting postsynaptic neurojunction, and toxins affecting ion channels. 
     
     
         18 . A composition according to  claim 17  wherein the toxin comprises α-cobratoxin. 
     
     
         19 . A composition according to  claim 17  wherein the immunokine can bind one or more of a chemokine receptor protein, and a cellular cofactor for a cellular HIV receptor protein. 
     
     
         20 . A composition according to  claim 19  wherein the protein to which the immunokine of the invention binds comprises CD4. 
     
     
         21 . A composition according to  claim 19  wherein the protein to which the immunokine of the invention binds comprises CXCR4. 
     
     
         22 . A composition according to  claim 19  wherein the protein to which the immunokine of the invention binds comprises CCR5. 
     
     
         23 . A method of treatment of animals suffering from neurological disorders comprising administering to the animal a disease mitigating dosage of a detoxified and neurotropically active modified alpha-neurotoxin composition which targets nicotinic acetylcholine receptors. 
     
     
         24 . The method of  claim 23  wherein the detoxified and neurotropically active modified compositions comprises a fraction containing the alpha-neurotoxins. 
     
     
         25 . The method of  claim 23  wherein the alpha-neurotoxins are selected from the group consisting of alpha-bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin, alpha-cobrotoxin, alpha-conotoxins (G1, M1, S1, S1A, ImI), alpha-dendrotoxin and erabutoxin. 
     
     
         26 . The method of  claim 23  wherein the alpha-neurotoxin composition comprises alpha-cobratoxin. 
     
     
         27 . The method of  claim 23  wherein composition administration methods include by injection (subcutaneous, intramuscular and intravenous), orally, optically and by intradermal routes. 
     
     
         28 . A method of vaccinating a subject comprising administering to the subject a immunogenic amount of a detoxified and neurotropically active modified neurotoxin composition with or without the inclusion of an adjuvant. 
     
     
         29 . The method of  claim 28  wherein composition administration methods include by injection (subcutaneous, intramuscular and intravenous), orally, optically and by intradermal routes. 
     
     
         30 . A composition comprising an administrable form of a detoxified and neurotropically active modified snake venom neurotoxin wherein a  Naja  venom neurotoxin is alpha-cobratoxin and the composition is atoxic. 
     
     
         31 . The composition of  claim 30 , wherein the alpha-cobratoxin can be administered orally when combined in a solution with benzalkonium chloride.