Messenger rna vaccines and uses thereof

Abstract

The present invention provides, among other things, methods and compositions of formulating nucleic acid-containing nanoparticles for efficient delivery of payload in vivo such that the method and compositions can be used to generate mRNA vaccines.

1 . A method of inducing an immune response in vivo comprising:
 administering to a subject in need thereof a composition comprising a messenger RNA (mRNA) encoding an antigen, encapsulated in a lipid nanoparticle, at a dosing regimen sufficient to induce an antigen specific T cell response and/or an antigen specific antibody response.   
     
     
         2 . The method of  claim 1 , wherein the composition is administered subcutaneously. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein
 the composition is a vaccine composition.   
     
     
         7 . A method of delivering a vaccine in vivo comprising:
 administering to a subject in need thereof a vaccine composition comprising a messenger RNA (mRNA) encoding an antigen, encapsulated in a lipid nanoparticle, wherein the vaccine composition is administered intramuscularly or subcutaneously.   
     
     
         8 . The method of  claim 7 , wherein the vaccine composition is administered at a dosing regimen sufficient to induce an antigen specific T cell response and/or an antigen specific antibody response. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of  claim 1 , wherein the composition comprises one or more mRNAs encoding one or more polypeptides. 
     
     
         12 . The method of  claim 1 , wherein the dosing regimen comprises injecting a single dose. 
     
     
         13 . The method of  claim 1 , wherein the dosing regimen comprises injecting multiple doses periodically. 
     
     
         14 - 19 . (canceled) 
     
     
         20 . The method of  claim 13 , wherein each of the multiple doses comprise a different dosage amount of mRNA. 
     
     
         21 - 23 . (canceled) 
     
     
         24 . The method of  claim 13 , wherein the multiple doses are injected at the following schedule: Dose 1 week 0, dose 2 in week 3, and dose 3 in week 5. 
     
     
         25 . The method of  claim 1 , wherein the mRNA comprises one or more modified nucleotides. 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 1 , wherein the lipid nanoparticle comprises one or more cationic lipids, one or more helper lipids, and one or more PEG lipids. 
     
     
         28 . (canceled) 
     
     
         29 . The method of  claim 27 , wherein the lipid nanoparticles comprises at least one cationic lipid selected from CCBene, ICE, ML-2, C12-200 or DLin-SS-DMA. 
     
     
         30 . The method of  claim 29 , wherein the at least one cationic lipid is ICE. 
     
     
         31 . The method of  claim 29 , wherein the at least one cationic lipid is ML-2. 
     
     
         32 . The method of  claim 29 , wherein the at least one cationic lipid is CCBene. 
     
     
         33 - 35 . (canceled) 
     
     
         36 . The method of  claim 1 , wherein the administration of the composition results in expression of the antigen encoded by mRNA in the lymphocytes of the subject. 
     
     
         37 . The method of  claim 1 , wherein the administration of the composition results in an antigen specific antibody response. 
     
     
         38 . The method of  claim 36 , wherein the antigen specific antibody response is measured by the presence of antigen-specific antibodies in serum. 
     
     
         39 . The method of  claim 1 , wherein the administration of the composition results in an antigen specific T-cell response. 
     
     
         40 . (canceled)