Uses of parasite macrophage migration inhibitory factors

Abstract

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection. The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen. The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as a Plasmodium parasite, or parasitic helminths.

1 . A composition for use in a method of providing protective immunity against a parasite infection in a subject in need thereof, which comprises an immunologically effective amount of one or more of:
 (i) a nucleic acid comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen;   (ii) a parasite MIF antigen; or   (iii) an antibody which specifically binds to a parasite MIF antigen.   
     
     
         2 . The composition for use according to  claim 1  (i) wherein the composition comprises an RNA-based vaccine. 
     
     
         3 . The composition for use according to  claim 1  or  claim 2  wherein the protective immunity is characterized by protective immunological memory against the parasite and/or an effective parasite-responsive memory T cell population. 
     
     
         4 . The composition for use according to  claim 1 ,  2  or  3  wherein the composition comprises a nucleic acid-based vaccine comprising the nucleic acid sequence which encodes a parasite MIF antigen; for example, wherein the nucleic acid-based vaccine is a RNA-based vaccine, which may comprises a self-replicating RNA molecule, such as an alphavirus-derived RNA replicon. 
     
     
         5 . The composition for use according to any preceding claim wherein the composition comprises a cationic nano-emulsion (CNE) delivery system or a lipid nanoparticle (LNP) delivery system. 
     
     
         6 . The composition for use according to any preceding claim wherein the composition comprises one or more adjuvants. 
     
     
         7 . The composition for use according to  claim 1  wherein the antibody which specifically binds to a parasite MIF antigen comprises monoclonal antibody or polyclonal antibody. 
     
     
         8 . The composition for use according to  claim 1  wherein the antibody which specifically binds to a parasite MIF antigen is a human, humanized or chimeric monoclonal antibody. 
     
     
         9 . The composition for use according to any preceding claim wherein the parasite is a parasitic protozoan, for example wherein (i) the protozoan is an apicomplexan parasite; and/or (ii) the protozoan belongs to a genus selected from the group consisting of:  Plasmodium, Toxoplasma, Babesia, Eimeria, Theileria, Neospora, Sarcocystis, Leishmania , and  Trypanosoma.    
     
     
         10 . The composition for use according to any one of  claims 1  to  8  wherein the parasite is a parasitic helminth, such as a nematode. 
     
     
         11 . The composition for use according to  claim 10  wherein the parasitic helminth belongs to a genus selected from the group consisting of:  Ancyclostoma, Necator, Brugia, Wuchereria, Loa, Mansonella, Trichinella, Trichuris, Ascaris, Anisakis, Dracunculus, Strongyloides, Haemonchus, Schistosoma  and  Fasciola.    
     
     
         12 . The composition for use according to any preceding claim wherein the subject is a vertebrate, such as a mammal e.g. a human or a veterinary mammal. 
     
     
         13 . The composition for use according to any preceding claim wherein:
 (a) the composition further comprises a nucleic acid sequence which encodes an additional parasite antigen, and/or   (b) the composition further comprises an additional parasite antigen, and/or   (c) the composition is administered to the subject in combination with a further composition which comprises a nucleic acid comprising a sequence which encodes an additional parasite antigen; and/or   (d) the composition is administered to the subject in combination with a further composition which comprises an additional parasite antigen.   
     
     
         14 . A composition comprising an immunologically effective amount of:
 (i) a nucleic acid comprising a sequence which encodes a parasite MIF antigen; or   (ii) a parasite MIF antigen;   wherein the MIF antigen is from:   (a) a parasitic protozoan; or   (b) a parasitic helminth which belongs to a genus selected from the group consisting of:  Ancyclostoma, Necator, Brugia, Wuchereria, Loa, Mansonella, Trichinella, Trichuris, Ascaris, Anisakis, Dracunculus, Strongyloides, Haemonchus, Schistosoma  and  Fasciola.      
     
     
         15 . The composition of  claim 14  wherein the parasitic protozoan is an apicomplexan parasite and/or belongs to a genus selected from the group consisting of:  Plasmodium, Toxoplasma, Babesia, Eimeria, Theileria, Neospora, Sarcocystis, Leishmania , and  Trypanosoma.    
     
     
         16 . The composition of any one of  claims 14  to  15  wherein the parasite MIF antigen is a full-length MIF polypeptide or an immunogenic fragment thereof. 
     
     
         17 . The composition of any one of  claims 14  to  16  which comprises a nucleic acid-based vaccine comprising the nucleic acid sequence which encodes a parasite MIF antigen; for example, wherein the nucleic acid-based vaccine is a RNA-based vaccine, such as a self-replicating RNA molecule, which may be an alphavirus-derived RNA replicon. 
     
     
         18 . The composition of any one of  claims 14  to  17  which comprises a cationic nano-emulsion (CNE) delivery system or a lipid nanoparticle (LNP) delivery system.