High potency immunogenic zika virus compositions
Provided herein, in some embodiments, are Zika Virus immunogenic compositions that include a cationic lipid nanoparticle (LNP) encapsulating messenger ribonucleic acid (mRNA) having an open reading frame encoding Zika Virus antigens, a pan HLA DR-binding epitope (PADRE), and a 5′ terminal cap modified to increase mRNA translation efficiency.
1. An immunogenic composition, 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.
2. 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.
3. The immunogenic composition of claim 1 , wherein the ZIKV prM antigen and the ZIKV E antigen form a fusion antigen comprising a sequence identified by SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6.
4. The immunogenic composition of claim 1 , wherein the open reading frame is codon optimized.
5. The immunogenic composition of claim 1 , wherein at least 80% of the uracil in the open reading frame has a chemical modification.
6. The immunogenic composition of claim 5 , wherein the chemical modification is N1-methylpseudouridine or N1-ethylpseudouridine.
7. The immunogenic composition of claim 5 , wherein the chemical modification is at the carbon 5-position of the uracil.
8. The immunogenic composition of claim 1 , wherein the 5′ terminal cap is 7mG(5′)ppp(5′)N1mpNp.
9. The immunogenic composition of claim 1 , wherein the open reading frame of the mRNA further encodes a signal sequence.
10. The immunogenic composition of claim 9 , wherein the signal sequence is the Japanese encephalitis prM signal sequence MWLVSLAIVTACAGA shown in SEQ ID NO: 11.
11. The immunogenic composition of claim 1 , 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.
12. The immunogenic composition of claim 1 , wherein the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
13. The immunogenic composition of claim 1 , wherein the cationic lipid nanoparticle comprises a compound of Formula (I).
14. The immunogenic composition of claim 13 , wherein the cationic lipid nanoparticle comprises Compound 1 or Compound 2.
15. A method of inducing an immune response in a subject, the method comprising administering to the subject the immunogenic composition of claim 1 in an amount effective to produce an antigen-specific immune response in the subject.
16. The immunogenic composition of claim 2 , wherein the ZIKV prM antigen and the ZIKV E antigen form a fusion antigen comprising a sequence identified by SEQ ID NO: 2, SEQ ID NO: 4, or SEQ ID NO: 6.
17. The immunogenic composition of claim 2 , wherein the ratio of mRNA encoding ZIKV antigen to mRNA encoding PADRE is 0.1:1 to 10:1.
18. The immunogenic composition of claim 2 , wherein at least one of the open reading frames is codon optimized.
19. The immunogenic composition of claim 2 , wherein at least 80% of the uracil in at least one of the open reading frames has a chemical modification.
20. The immunogenic composition of claim 19 , wherein the chemical modification is N1-methylpseudouridine or N1-ethylpseudouridine.
21. The immunogenic composition of claim 19 , wherein the chemical modification is at the carbon 5-position of the uracil.
22. The immunogenic composition of claim 2 , wherein at least one of the 5′ terminal caps is 7mG(5′)ppp(5′)N1mpNp.
23. The immunogenic composition of claim 2 , wherein at least one of the open reading frames of the mRNA further encodes a signal sequence.
24. The immunogenic composition of claim 23 , wherein the signal sequence is the Japanese encephalitis prM signal sequence MWLVSLAIVTACAGA shown in SEQ ID NO: 11.
25. The immunogenic composition of claim 2 , 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.
26. The immunogenic composition of claim 2 , wherein the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
27. The immunogenic composition of claim 2 , wherein the cationic lipid nanoparticle comprises a compound of Formula (I).
28. The immunogenic composition of claim 27 , wherein the cationic lipid nanoparticle comprises Compound 1 or Compound 2.