Papaya mosaic virus compositions and uses thereof for stimulation of the innate immune response

Abstract

The use of compositions comprising a papaya mosaic virus (PapMV) moiety for stimulation of the innate immune response is provided. The PapMV moiety may be papaya mosaic virus or PapMV virus-like particles (VLPs). The PapMV compositions stimulate a sufficiently strong innate immune response to provide protection against subsequent pathogen challenge or to treat an established infection. The use of PapMV compositions to protect a subject from potential infection by a pathogen, such as a viral pathogen, a bacterial pathogen or a fungal pathogen, and the use of PapMV compositions to treat an established infection, are also provided. The PapMV compositions be administered, for example, via intranasal or pulmonary routes to elicit effects within the mucosa and/or in the respiratory system.

1 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) to stimulate an innate immune response in a subject and thereby prevent, or decrease the severity of, a microbial infection in the subject. 
     
     
         2 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) in the manufacture of a medicament to stimulate an innate immune response in a subject and thereby prevent, or decrease the severity of, a microbial infection in the subject. 
     
     
         3 . The use according to  claim 1  or  2 , wherein the microbial infection is an infection with a microorganism that gains access to the subject's body via mucosal membranes. 
     
     
         4 . The use according to any one of  claims 1  to  3 , wherein the microbial infection is a viral infection. 
     
     
         5 . The use according to any one of  claims 1  to  3 , wherein the microbial infection is a bacterial infection. 
     
     
         6 . The use according to any one of  claims 1  to  5 , for preventing a microbial infection in the subject. 
     
     
         7 . The use according to any one of  claims 1  to  5 , for decreasing the severity of a microbial infection in the subject. 
     
     
         8 . The use according to any one of  claims 1  to  7 , wherein the immune response is stimulated at a mucosal surface. 
     
     
         9 . The use according to  claim 8 , wherein the composition is for administration with one or more antigens. 
     
     
         10 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) to protect a subject against infection with a pathogen, wherein the composition stimulates the innate immune response in the subject. 
     
     
         11 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) in the manufacture of a medicament to protect a subject against infection with a pathogen, wherein the composition stimulates the innate immune response in the subject. 
     
     
         12 . The use according to  claim 10  or  11 , wherein the pathogen is a microorganism that gains access to the subject's body via mucosal membranes. 
     
     
         13 . The use according to any one of  claims 10  to  12 , wherein the pathogen is a virus. 
     
     
         14 . The use according to  claim 13 , wherein the virus is an influenza virus, flavivirus, parainfluenza virus, respiratory syncytial virus, coronavirus, adenovirus or rhinovirus. 
     
     
         15 . The use according to any one of  claims 10  to  12 , wherein the pathogen is a bacteria. 
     
     
         16 . The use according to  claim 15 , wherein the bacteria is  Bacillus anthraces, Yersinia pestis, Francisella tularensis, Streptococcus pnemoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, Corynebacterium diphtheriae, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Mycobacterium tuberculosis, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli  or  Coxiella burnetii.    
     
     
         17 . The use according to any one of  claims 10  to  16 , wherein the composition is for administration between 4 hours and 6 days prior to expected exposure of the subject to the pathogen. 
     
     
         18 . The use according to any one of  claims 10  to  16 , wherein the composition is for administration in multiple doses. 
     
     
         19 . The use according to any one of  claims 10  to  18 , wherein the subject is immunocompromised, undergoing chemotherapy or taking immunosuppressive drugs. 
     
     
         20 . The use according to any one of  claims 10  to  19 , wherein the composition prevents immune exhaustion in the subject. 
     
     
         21 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) to treat a chronic or recurrent microbial infection in a subject. 
     
     
         22 . Use of a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs) in the manufacture of a medicament to treat a chronic or recurrent microbial infection in a subject. 
     
     
         23 . The use according to  claim 21  or  22 , wherein the composition is for administration in combination with one or more conventional therapies. 
     
     
         24 . The use according to any one of  claims 21  to  23 , wherein the microbial infection is a bacterial infection. 
     
     
         25 . The use according to any one of  claims 21  to  23 , wherein the microbial infection is a viral infection. 
     
     
         26 . The use according to  claim 25 , wherein the viral infection is a hepatitis C virus infection or human immunodeficiency virus infection. 
     
     
         27 . The use according to  claim 25  or  26 , wherein the composition decreases viral load in the subject. 
     
     
         28 . The use according to any one of  claims 1  to  27 , wherein the composition is for intranasal administration. 
     
     
         29 . The use according to any one of  claims 1  to  28 , wherein the composition comprises PapMV. 
     
     
         30 . The use according to any one of  claims 1  to  28 , wherein the composition comprises PapMV VLPs. 
     
     
         31 . The use according to  claim 30 , wherein the PapMV VLPs comprise ssRNA. 
     
     
         32 . A method of stimulating an innate immune response in a subject comprising administering to the subject an effective amount of a composition comprising  papaya mosaic  virus (PapMV) or PapMV virus-like particles (VLPs), thereby preventing, or decreasing the severity of, a microbial infection in the subject. 
     
     
         33 . The method according to  claim 32 , wherein the microbial infection is an infection with a microorganism that gains access to the subject's body via mucosal membranes. 
     
     
         34 . The method according to  claim 32 , wherein the microbial infection is a viral infection. 
     
     
         35 . The method according to  claim 32 , wherein the microbial infection is a bacterial infection. 
     
     
         36 . The method according to  claim 32 , for preventing a microbial infection in the subject. 
     
     
         37 . The method according to  claim 32 , for decreasing the severity of a microbial infection in the subject. 
     
     
         38 . The method according to  claim 32 , wherein the immune response is stimulated at a mucosal surface. 
     
     
         39 . The method according to  claim 38 , wherein the composition is administered with one or more antigens. 
     
     
         40 . The method according to  claim 32 , wherein the composition is administered via an intranasal route. 
     
     
         41 . The method according to  claim 32 , wherein the composition comprises PapMV. 
     
     
         42 . The method according to  claim 32 , wherein the composition comprises PapMV VLPs. 
     
     
         43 . The method according to  claim 42 , wherein the PapMV VLPs comprise ssRNA. 
     
     
         44 . A method of protecting a subject against microbial infection comprising administering to the subject an effective amount of a composition comprising  papaya mosaic  virus (PapMV) or PapMV virus-like particles (VLPs), wherein the composition stimulates the innate immune response in the subject. 
     
     
         45 . The method according to  claim 44 , wherein the microbial infection is an infection with a microorganism that gains access to the subject's body via mucosal membranes. 
     
     
         46 . The method according to  claim 44 , wherein the microbial infection is a viral infection. 
     
     
         47 . The method according to  claim 46 , wherein the viral infection is an influenza, flavivirus, parainfluenza virus, respiratory syncytial virus, coronavirus, adenovirus or rhinovirus infection. 
     
     
         48 . The method according to  claim 44 , wherein the microbial infection is a bacterial infection. 
     
     
         49 . The method according to  claim 48 , wherein the bacterial infection is a  Bacillus anthraces, Yersinia pestis, Francisella tularensis, Streptococcus pnemoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia, Corynebacterium diphtheriae, Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Mycobacterium tuberculosis, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli  or  Coxiella burnetii  infection. 
     
     
         50 . The method according to  claim 44 , wherein the composition is administered to the subject between 4 hours and 6 days prior to expected exposure of the subject to the pathogen. 
     
     
         51 . The method according to  claim 44 , wherein the composition is administered to the subject in multiple doses. 
     
     
         52 . The method according to  claim 44 , wherein the subject is immunocompromised, undergoing chemotherapy or taking immunosuppressive drugs. 
     
     
         53 . The method according to  claim 44 , wherein the composition prevents immune exhaustion in the subject. 
     
     
         54 . The method according to  claim 44 , wherein the composition is administered via an intranasal route. 
     
     
         55 . The method according to  claim 44 , wherein the composition comprises PapMV. 
     
     
         56 . The method according to  claim 44 , wherein the composition comprises PapMV VLPs. 
     
     
         57 . The method according to  claim 56 , wherein the PapMV VLPs comprise ssRNA. 
     
     
         58 . A method of treating a chronic or recurrent infection comprising administering to a subject having a chronic microbial infection a composition comprising  Papaya Mosaic  Virus (PapMV) or PapMV virus-like particles (VLPs). 
     
     
         59 . The method according to  claim 58 , wherein the composition is administered in combination with one or more conventional therapies. 
     
     
         60 . The method according to  claim 58 , wherein the microbial infection is a bacterial infection. 
     
     
         61 . The method according to  claim 58 , wherein the microbial infection is a viral infection. 
     
     
         62 . The method according to  claim 61 , wherein the viral infection is a hepatitis C virus infection or human immunodeficiency virus infection. 
     
     
         63 . The method according to  claim 58 , wherein the composition decreases viral load in the subject. 
     
     
         64 . The method according to  claim 58 , wherein the composition is administered via an intranasal route. 
     
     
         65 . The method according to  claim 58 , wherein the composition comprises PapMV. 
     
     
         66 . The method according to  claim 58 , wherein the composition comprises PapMV VLPs. 
     
     
         67 . The method according to  claim 66 , wherein the PapMV VLPs comprise ssRNA. 
     
     
         68 . A kit comprising a container having contained therein a pharmaceutical composition comprising  papaya mosaic  virus (PapMV) or PapMV virus-like particles (VLPs), the container adapted to deliver the pharmaceutical composition by an intranasal, pulmonary or vaginal route. 
     
     
         69 . The kit according to  claim 68 , wherein the container is an inhaler, nebulizer or nasal spray device.