Methods and compositions to modulate antiviral and immune activity responses

Abstract

The invention is directed to an improved method to manufacture virus for use in vaccine by culturing infected cells that have been modified to overexpress miR-144. The invention is also directed to manipulating the activity or level of miR-144 in subjects in order to modulate the antiviral and immune response systems.

1 . A vaccine prepared by formulating a virus or a component thereof, wherein said virus has been obtained by a process that comprises culturing host cells infected with said virus and modified to overexpress miR-144, and
 recovering said virus from the cells.   
     
     
         2 . The vaccine of  claim 1  wherein said process further comprises inactivating said recovered virus. 
     
     
         3 . The vaccine of  claim 1  wherein said process further comprises isolating said component from the recovered virus. 
     
     
         4 . The vaccine of  claim 1  wherein the host cells are epithelial cells. 
     
     
         5 . Recombinant host cells that have been modified to contain an expression system for miR-144. 
     
     
         6 . The cells of  claim 5  which are further infected with virus. 
     
     
         7 . The cells of  claim 5  which are epithelial cells. 
     
     
         8 . A method to modulate the immune system or the antiviral response of a subject which comprises either
 (a) increasing the level of immune activity or antiviral response by decreasing the level or activity of miR-144 in said subject or   (b) decreasing immune activity or antiviral response by increasing the level or activity of miR-144 in said subject.   
     
     
         9 . The method of  claim 8  which method comprises increasing immune activity or antiviral response, wherein the method comprises:
 administering to said subject an antisense nucleic acid complementary to miR-144, or 
 administering to said subject short interfering RNA (siRNA) having a nucleotide sequence corresponding to miR-144, or 
 suppressing endogenous transcription of the gene which produces miRNA, or 
 administering to said individual an antibody or fragment immunoreactive with miR-144 or a mimetic that specifically reacts with miR-144. 
 
     
     
         10 . The method of  claim 9 , wherein said subject is infected by an infectious agent. 
     
     
         11 . The method of  claim 10  wherein the infectious agent is a bacteria, a fungus, a virus or a protozoan. 
     
     
         12 . The method of  claim 8  which method comprises decreasing the immune activity or antiviral response in said subject,
 wherein the method comprises administering a nucleic acid with the nucleotide sequence of miR-144 to the subject, or 
 administering a nucleic acid that comprises an expression system that produces miR-144 to the subject. 
 
     
     
         13 . The method of  claim 12  wherein the expression system is included in a viral vector. 
     
     
         14 . The method of  claim 12  wherein said subject is afflicted with an autoimmune disease or suffers from inflammation. 
     
     
         15 . A nucleic acid molecule which is a modified nucleic acid comprising a nucleotide sequence complementary to miR-144, or
 is short interfering RNA having a nucleotide sequence corresponding to miR-144, or   is a modified nucleic acid comprising the nucleotide sequence of miR-144.   
     
     
         16 . The nucleic acid of  claim 15  formulated as a pharmaceutical or veterinary composition. 
     
     
         17 . The composition of  claim 16  formulated for nasal administration. 
     
     
         18 . A recombinant vector that generates an RNA complementary to miR-144, or an RNA comprising the nucleotide sequence of miR-144 or short interfering RNA that decreases the level of miR-144. 
     
     
         19 . The vector of  claim 18  that is a viral vector. 
     
     
         20 . A composition of matter which is an antibody, mimetic or aptamer that specifically binds miR-144. 
     
     
         21 . The composition of matter of  claim 20  formulated as a pharmaceutical.