Method for preparing viral particles with cyclic dinucleotide and use of said particles for inducing immune response

Abstract

The present invention relates to methods for preparing virus-like particles comprising immunogenic cyclic dinucleotides.

We claim: 
     
         1 . A virus-like particle comprising a lipoprotein envelope comprising a viral fusogenic glycoprotein, wherein said virus-like particle contains cyclic dinucleotides packaged into said virus-like particle. 
     
     
         2 . The virus-like particle according to  claim 1 , wherein the virus-like particle further comprises a capsid from retroviridae. 
     
     
         3 . The virus-like particle according to  claim 1 , wherein the viral fusogenic glycoprotein is a glycoprotein from retroviridae, herpesviridae, poxviridae, hepadnaviridae, flaviviridae, togavoridae, coronaviridae, hepatitis D virus, orthomyxoviridae, paramyxoviridae, filoviridae, rhabdoviridae, bunyaviridae, or orthopoxivridae. 
     
     
         4 . The virus-like particle according to  claim 3 , wherein the viral fusogenic glycoprotein is a glycoprotein from lentivirus, retrovirus, variola virus, orthomyxovirus, retroviruses, or rhabdovirus. 
     
     
         5 . The virus-like particle according to  claim 1 , wherein the viral fusogenic glycoprotein is a glycoprotein from HIV (Human Immunodeficiency Virus), HIV-1 HIV-2, Influenza virus, thogotovirus, or VSV (Vesicular Stomatitis Virus). 
     
     
         6 . The virus-like particle according to  claim 2 , wherein the retroviral capsid is from retroviridae. 
     
     
         7 . The virus-like particle according to  claim 6 , wherein the retroviral capsid is a lentivirus or retrovirus capsid. 
     
     
         8 . The virus-like particle according to  claim 2 , wherein the retroviral capsid is from HIV or MLV (Murine Leukemia Virus). 
     
     
         9 . The virus-like particle according to  claim 1 , wherein the cyclic dinucleotides are selected from the group consisting of cyclic di-adenosine monophosphate (c-di-AMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). 
     
     
         10 . The virus-like particle according to  claim 1 , wherein it further comprises an antigen or other protein or nucleic acid of interest. 
     
     
         11 . A pharmaceutical, vaccine or veterinary composition comprising a virus-like particle according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . The pharmaceutical, vaccine or veterinary composition according to  claim 11 , wherein it further comprises an antigen or a therapeutically active agent. 
     
     
         13 . A method for inducing or enhancing an immune response in a subject comprising administrating a virus-like particle according to  claim 1  or a composition thereof. 
     
     
         14 . A method for preventing or treating an infectious disease or a cancer in a subject comprising administrating a virus-like particle according to  claim 1  or a composition thereof. 
     
     
         15 . A method for preparing a virus-like particle comprising cyclic dinucleotides packaged into said virus-like particle, wherein the method comprises:
 co-expression of a cyclic dinucleotide synthase and a viral fusogenic glycoprotein in an eukaryotic cell in conditions allowing the synthesis of cyclic dinucleotides and the viral fusogenic glycoprotein in said cell; and   recovering of the virus-like particles produced by said cell.   
     
     
         16 . The method according to  claim 15 , wherein the cyclic dinucleotide synthase is selected from the group consisting of the diadenylate cyclase, diguanylate cyclase and the cyclic GMP-AMP synthase.