High potency immunogenic compositions

Abstract

Provided herein, in some embodiments, are immunogenic compositions that include a cationic lipid nanoparticle (LNP) encapsulating messenger ribonucleic acid (mRNA) having an open reading frame encoding a viral, bacterial or parasitic antigen, a pan HLA DR-binding epitope (PADRE), and a 5′ terminal cap modified to increase mRNA translation efficiency.

1 .- 30 . (canceled) 
     
     
         31 . A method of inducing an immune response in a subject, the method comprising administering to the subject an immunogenic composition of comprising a cationic lipid nanoparticle (LNP) encapsulating messenger ribonucleic acid (mRNA) having an open reading frame encoding a Zika virus (ZIKV) prM antigen, a ZIKV E antigen, and a pan HLA DR-binding epitope (PADRE), and a 5′ terminal cap, wherein the cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol, and a non-cationic lipid, in an amount effective to produce in the subject an immune response specific to ZIKV prM antigen and/or ZIKV E antigen. 
     
     
         32 .- 105 . (canceled) 
     
     
         106 . The method of  claim 31 , wherein the ZIKV prM antigen and the ZIKV E antigen form a fusion antigen comprising a sequence set forth in SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6. 
     
     
         107 . The method of  claim 31 , wherein the open reading frame is codon optimized. 
     
     
         108 . The method of  claim 31 , wherein at least 80% of the uracil in the open reading frame has a chemical modification. 
     
     
         109 . The method of  claim 108 , wherein the chemical modification is N1-methylpseudouridine or N1-ethylpseudouridine. 
     
     
         110 . The method of  claim 108 , wherein the chemical modification is at the carbon 5-position of the uracil. 
     
     
         111 . The method of  claim 31 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)N1mpNp. 
     
     
         112 . The method of  claim 31 , wherein the open reading frame of the mRNA further encodes a signal sequence. 
     
     
         113 . The method of  claim 112 , wherein the signal sequence is the Japanese encephalitis prM signal sequence set forth in SEQ ID NO: 11. 
     
     
         114 . The method of  claim 31 , wherein the cationic lipid nanoparticle comprises a molar ratio of 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid. 
     
     
         115 . The method of  claim 31 , wherein the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. 
     
     
         116 . The method of  claim 31 , wherein the cationic lipid nanoparticle comprises a compound of Formula (I). 
     
     
         117 . The method of  claim 116 , wherein the cationic lipid nanoparticle comprises Compound 1 or Compound 2. 
     
     
         118 . The method of  claim 31 , wherein the amount administered is 5 μg to 100 μg of the mRNA. 
     
     
         119 . A method of inducing an immune response in a subject, the method comprising administering to the subject an immunogenic composition comprising a cationic lipid nanoparticle (LNP) encapsulating (a) a messenger ribonucleic acid (mRNA) having an open reading frame encoding a Zika virus (ZIKV) prM antigen, a ZIKV E antigen, and a 5′ terminal cap; and (b) a mRNA having an open reading frame encoding a pan HLA DR-binding epitope (PADRE), and a 5′ terminal cap, wherein the cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid, in an amount effective to produce in the subject an immune response specific to ZIKV prM antigen and/or ZIKV E antigen. 
     
     
         120 . The method of  claim 119 , wherein the ZIKV prM antigen and the ZIKV E antigen form a fusion antigen comprising a sequence set forth in SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6. 
     
     
         121 . The method of  claim 119 , wherein the open reading frame of (a) and/or the open reading frame of (b) are codon optimized. 
     
     
         122 . The method of  claim 119 , wherein at least 80% of the uracil in the open reading frame of (a) has a chemical modification, and/or at least 80% of the uracil in the open reading frame of (b) has a chemical modification. 
     
     
         123 . The method of  claim 122 , wherein the chemical modification of (a) and/or (b) is N1-methylpseudouridine or N1-ethylpseudouridine. 
     
     
         124 . The method of  claim 122 , wherein the chemical modification of (a) and/or (b) is at the carbon 5-position of the uracil. 
     
     
         125 . The method of  claim 119 , wherein the 5′ terminal cap of (a) and/or (b) is 7mG(5′)ppp(5′)N1mpNp. 
     
     
         126 . The method of  claim 119 , wherein the open reading frame of (a) and/or (b) further encodes a signal sequence. 
     
     
         127 . The method of  claim 126 , wherein the signal sequence is the Japanese encephalitis prM signal sequence set forth in SEQ ID NO: 11. 
     
     
         128 . The method of  claim 119 , wherein the cationic lipid nanoparticle comprises a molar ratio of 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid. 
     
     
         129 . The method of  claim 119 , wherein the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. 
     
     
         130 . The method of  claim 119 , wherein the cationic lipid nanoparticle comprises a compound of Formula (I). 
     
     
         131 . The method of  claim 130 , wherein the cationic lipid nanoparticle comprises Compound 1 or Compound 2. 
     
     
         132 . The method of  claim 119 , wherein the amount administered is 5 μg to 100 μg of the mRNA.