Administration of interferon for prophylaxis against or treatment of pathogenic infection

Abstract

The invention provides compositions and methods for the prophylaxis or treatment of diseases or disorders in a subject (e.g., a mammal, such as a human) including, e.g., diseases or disorders caused by biological agents, autoimmune diseases, and cancer. The compositions include a delivery vector (e.g., a viral vector, such as an Ad5 vector) encoding an interferon (e.g., IFN-α), and are provided to the subject by, e.g., intranasal or pulmonary administration.

What is claimed is: 
     
         1 . A composition comprising a vector comprising a nucleic acid molecule encoding an interferon (IFN), wherein said composition is formulated as:
 a) a dry, lyophilized powder, gel, or liquid, wherein said composition is stable at room temperature for at least one week; or   b) a frozen, non-stabilized liquid, wherein said composition, once thawed, is stable at room temperature for at least 24 hours.   
     
     
         2 . The composition of  claim 1 , wherein said interferon is IFN-alpha (IFN-α). 
     
     
         3 . The composition of  claim 2 , wherein said IFN-α is consensus IFN-α (conIFN-α). 
     
     
         4 . The composition of  claim 1 , wherein said vector is a viral or non-viral vector. 
     
     
         5 . The composition of  claim 4 , wherein said viral vector is an adenoviral vector. 
     
     
         6 . The composition of  claim 5 , wherein said adenoviral vector is an adenoviral 5 (Ad5) vector. 
     
     
         7 . The composition of  claim 6 , wherein said Ad5 vector is a replication deficient vector that comprises deletions of the E1 and E3 genes. 
     
     
         8 . The composition of  claim 1 , wherein said nucleic acid molecule of said vector is operably linked to a promoter selected from an SV40 promoter, CMV promoter, adenovirus early and late promoter, metallothioneine gene (MT-1) promoter, Rous sarcoma virus (RSV) promoter, and human Ubiquitine C (UbC) promoter. 
     
     
         9 . The composition of  claim 1 , wherein said vector further comprises one or more of a signal sequence, a polyadenylation sequence, and enhancer, an upstream activation sequence, and a transcription termination factor that facilitates expression of said nucleic acid molecule encoding said interferon. 
     
     
         10 . The composition of  claim 3 , wherein said conIFN-α encoded by said nucleic acid molecule has a polypeptide sequence comprising the sequence set forth in SEQ ID NO: 11. 
     
     
         11 . The composition of  claim 1 , wherein said composition further comprises a pharmaceutically acceptable excipient selected from one or more of fructose, maltose, galactose, glucose, D-mannose, sorbose, lactose, sucrose, trehalose, cellobiose, raffinose, melezitose, maltodextrins, dextrans, starches, mannitol, xylitol, xylose, maltitol, lactitol, xylitol sorbitol, sorbitose, pyranosyl sorbitol, myoinositol, glycine, CaCl 2 , hydroxyectoine, ectoine, gelatin, di-myo-inositol phosphate (DIP), cyclic 2,3 diphosphoglycerate (cDPG), 1,1-di-glycerol phosphate (DGP), β-mannosylglycerate (firoin), β-mannosylglyceramide (firoin A), and proline betaine. 
     
     
         12 . The composition of  claim 1 , wherein said composition is formulated for aerosolized delivery. 
     
     
         13 . The composition of  claim 1 , wherein said composition is stable at room temperature for at least one month to at least 1 year. 
     
     
         14 . The composition of  claim 1 , wherein said composition is admixed with a pharmaceutically acceptable liquid to form said liquid or gel. 
     
     
         15 . The composition of  claim 1 , further comprising an additional therapeutic agent selected from an anti-viral agent, an anti-bacterial agent, an anti-fungal agent, an anti-parasitic agent, an immunostimulatory agent, a vaccine, and a chemotherapeutic agent. 
     
     
         16 . The composition of  claim 15 , wherein said vaccine is an Ebola virus vaccine. 
     
     
         17 . A method for treating or reducing the effects of an infection, autoimmune disease, or cancer in a subject in need thereof comprising administering an amount of the composition of  claim 1  to the pulmonary or nasal mucosa of the subject one or more times. 
     
     
         18 . The method of  claim 17 , wherein administration of said composition results in expression of said interferon (IFN) in pulmonary or nasal epithelial cells of said mucosa. 
     
     
         19 . The method of  claim 17 , wherein said composition comprises an adenoviral 5 (Ad5) vector encoding said IFN and said method comprises administering said Ad5 vector in an amount in the range of at least about 1×10 3  to about 1×10 14  viral particles per dose. 
     
     
         20 . The method of  claim 17 , wherein said IFN is IFN-α. 
     
     
         21 . The method of  claim 20 , wherein said IFN-α is consensus IFN-α (conIFN-α). 
     
     
         22 . The method of  claim 17 , wherein said subject receives said composition prior to or after exposure to said pathogen or diagnosis of said autoimmune disease or cancer. 
     
     
         23 . The method of  claim 22 , wherein said subject receives said composition at least 15 minutes to at least 1 week prior to exposure to said pathogen. 
     
     
         24 . The method of  claim 22 , wherein said subject receives said composition immediately after exposure to said pathogen or diagnosis of said autoimmune disease or cancer or at least 15 minutes to at least 48 hours after exposure to said pathogen or diagnosis of said autoimmune disease or cancer. 
     
     
         25 . The method of  claim 17 , wherein said pathogen is a bacterium, virus, fungus, or parasite. 
     
     
         26 . The method of  claim 25 , wherein:
 i) said bacterium is selected from  Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Klebsiella pneumoniae, Bruscella, Burkholderia mallei, Yersinia pestis , and  Bacillus anthraci;      ii) said virus is selected from a member of the Flaviviridae, Arenaviridae, Bunyaviridae, Filoviridae, Togaviridae, Poxyiridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Rhabdoviridae, Paramyxoviridae, Picornaviridae, Hepadnaviridae, Papillamoviridae, Parvoviridae, Astroviridae, Polyomaviridae, Calciviridae, Reoviridae, and the Retroviridae family;   iii) said fungus is selected from  Aspergillus, Blastomyces dermatitidis, Candida, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum  var.  capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Zygomycetes  spp.,  Absidia corymbifera, Rhizomucor pusillus , and  Rhizopus arrhizus ; or   iv) said parasite is selected from  Toxoplasma gondii, Plasmodium falciparum, P. vivax, P. ovale, P. malariae, Trypanosoma  spp., and  Legionella  spp.   
     
     
         27 . The method of  claim 26 , wherein said virus is selected from hepatitis C virus, Yellow fever virus, Gadgets Gully virus, Kadam virus, Kyasanur Forest disease virus, Langat virus, Omsk hemorrhagic fever virus, Powassan virus, Royal Farm virus, Karshi virus, tick-borne encephalitis virus, Neudoerfl virus, Sofjin virus, Louping ill virus, Negishi virus, Meaban virus, Saumarez Reef virus, Tyuleniy virus, Aroa virus, dengue virus, Kedougou virus, Cacipacore virus, Koutango virus, Japanese encephalitis virus, Murray Valley encephalitis virus, St. Louis encephalitis virus, Usutu virus, West Nile virus, Yaounde virus, Kokobera virus, Bagaza virus, Ilheus virus, Israel turkey meningoencephalo-myelitis virus, Ntaya virus, Tembusu virus, Zika virus, Banzi virus, Bouboui virus, Edge Hill virus, Jugra virus, Saboya virus, Sepik virus, Uganda S virus, Wesselsbron virus, yellow fever virus, Entebbe bat virus, Yokose virus, Apoi virus, Cowbone Ridge virus, Jutiapa virus, Modoc virus, Sal Vieja virus, San Perlita virus, Bukalasa bat virus, Carey Island virus, Dakar bat virus, Montana myotis leukoencephalitis virus, Phnom Penh bat virus, Rio Bravo virus, Tamana bat virus, Cell fusing agent virus, Ippy virus, Lassa virus, lymphocytic choriomeningitis virus (LCMV), Mobala virus, Mopeia virus, Amapari virus, Flexal virus, Guanarito virus, Junin virus, Latino virus, Machupo virus, Oliveros virus, Paraná virus, Pichinde virus, Pirital virus, Sabiá virus, Tacaribe virus, Tamiami virus, Whitewater Arroyo virus, Chapare virus, Lujo virus, Hantaan virus, Sin Nombre virus, Dugbe virus, Bunyamwera virus, Rift Valley fever virus, La Crosse virus, Punta Toro virus (PTV), California encephalitis virus, Crimean-Congo hemorrhagic fever (CCHF) virus, Ebola virus, Marburg virus, Venezuelan equine encephalitis virus (VEE), Eastern equine encephalitis virus (EEE), Western equine encephalitis virus (WEE), Sindbis virus, rubella virus, Semliki Forest virus, Ross River virus, Barmah Forest virus, O'nyong'nyong virus, chikungunya virus, smallpox virus, monkeypox virus, vaccinia virus, herpes simplex virus (HSV), human herpes virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella-Zoster virus, Kaposi's sarcoma associated-herpesvirus (KSHV), influenza virus, severe acute respiratory syndrome (SARS) virus, rabies virus, vesicular stomatitis virus (VSV), human respiratory syncytial virus (RSV), Newcastle disease virus, hendravirus, nipahvirus, measles virus, rinderpest virus, canine distemper virus, Sendai virus, human parainfluenza virus, rhinovirus, mumps virus, coxsackievirus, hepatitis B virus, human papilloma virus, adeno-associated virus, astrovirus, JC virus, BK virus, SV40 virus, Norwalk virus, rotavirus, human immunodeficiency virus (HIV), and human T-lymphotropic virus (HTLV). 
     
     
         28 . The method of  claim 17 , wherein said composition is inhaled as a lyophilized powder. 
     
     
         29 . The method of  claim 17 , wherein said composition is admixed with a pharmaceutically acceptable liquid and inhaled as an aerosolized mist. 
     
     
         30 . The method of  claim 29 , wherein said pharmaceutically acceptable liquid is water or saline. 
     
     
         31 . The method of  claim 17 , wherein said subject is a human. 
     
     
         32 . The method of  claim 17 , wherein said subject is administered at least 2 doses of said composition. 
     
     
         33 . The method of  claim 17 , wherein said composition is administered as a gel. 
     
     
         34 . The method of  claim 17 , wherein said method further comprises administering an additional therapeutic agent selected from an anti-viral agent, an anti-bacterial agent, an anti-fungal agent, an anti-parasitic agent, an immunostimulatory agent, a vaccine, and a chemotherapeutic agent. 
     
     
         35 . The method of  claim 34 , wherein said vaccine is an Ebola virus vaccine. 
     
     
         36 . The method of  claim 34 , wherein said therapeutic agent is administered separately or concurrently with said composition. 
     
     
         37 . The method of  claim 34 , wherein said therapeutic agent is admixed with said composition. 
     
     
         38 . A device comprising the composition of  claim 1 , wherein said device comprises:
 a) a container comprising said composition;   b) a nozzle for directing said composition to the pulmonary or nasal mucosa of a subject;   c) a mechanical delivery pump for delivering the composition to the nozzle, wherein activation of said pump results in a fluid connection between said nozzle and said container; and   d) an actuation mechanism for activating said mechanical delivery pump.   
     
     
         39 . The device of  claim 38 , wherein the actuation mechanism comprises a trigger for actuating the delivery pump at a predeterminable pressure or flow rate. 
     
     
         40 . The device of  claim 38 , wherein the delivery pump comprises a liquid delivery pump for delivering a metered volume of said composition in liquid or powder form. 
     
     
         41 . The device of  claim 38 , wherein the nozzle is configured to deliver an aerosol or a jet. 
     
     
         42 . A kit comprising
 i) a first container comprising a composition comprising a vector comprising a nucleic acid molecule encoding an interferon (IFN), wherein said composition is formulated as:
 a) a dry, lyophilized powder, gel, or liquid, wherein said composition is stable at room temperature for at least one week; or 
 b) a frozen, non-stabilized liquid, wherein said composition, once thawed, is stable at room temperature for at least 24 hours; 
   ii) a second container comprising a pharmaceutically acceptable liquid; and   iii) the device of  claim 38  and, optionally, instructions for using the device to deliver the contents of said first container, or for combining the contents of said first and second containers to form a combined composition and then using the device to deliver the combined composition, to a subject for treating or inhibiting infection by a pathogen.