Nucleic acid vaccines
View Patent ↗The invention relates to compositions and methods for the preparation, manufacture and therapeutic use ribonucleic acid vaccines (NAVs) comprising polynucleotide molecules encoding one or more antigens.
1. A nucleic acid vaccine, comprising:
one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein selected from H1, H7 and H10 wherein the hemagglutinin protein is derived from a strain of Influenza A virus, wherein the RNA polynucleotide includes a chemical modification and a pharmaceutically acceptable carrier or excipient, formulated within a lipid nanoparticle, wherein the lipid nanoparticle has about 20-60 mol % ionizable cationic lipid; about 5-25 mol % non-cationic lipid; about 25-55 mol % sterol; and about 0.5-15 mol % PEG-modified lipid.
2. The vaccine of claim 1 , wherein the RNA polynucleotide does not encode F protein.
3. The vaccine of claim 1 , wherein the RNA polynucleotide further encodes an influenza neuraminidase protein.
4. The vaccine of claim 1 , wherein the Influenza virus is selected from H1N1, H7N9, and H10N8.
5. The vaccine of claim 1 wherein the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methoxyuridine, and 2′-O-methyl uridine.
6. The vaccine of claim 1 , wherein the ionizable cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319).
7. The vaccine of claim 1 , wherein the RNA polynucleotide comprises at least one of SEQ ID Nos 941-945.
8. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide having at least 80% sequence identity to at least one of SEQ ID NOs 941-945.
9. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 941.
10. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 941.
11. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 946.
12. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 946.
13. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to at least one of SEQ ID NO 946-950.
14. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of at least one of SEQ ID NO 946-950.
15. The vaccine of claim 1 , wherein the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 395.
16. The vaccine of claim 1 , wherein the RNA polynucleotide comprises 80-95% sequence identity to SEQ ID NO 394.
17. The vaccine of claim 1 , wherein the RNA polynucleotide comprises SEQ ID NO: 395.
18. The vaccine of claim 1 , wherein the lipid nanoparticle comprises a molar ratio of about 40-60 mol % ionizable cationic lipid, about 1-2 mol % PEG lipid, about 30-50 mol % cholesterol and about 5-15 mol % non-cationic lipid.
19. The vaccine of claim 1 , wherein the open reading frame is codon-optimized.
20. The vaccine of claim 1 , wherein the hemagglutinin protein is H1.
21. The vaccine of claim 1 , wherein the hemagglutinin protein is H7.
22. The vaccine of claim 1 , wherein the hemagglutinin protein is H10.
23. A nucleic acid immunogenic composition, comprising:
one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein selected from H1, H7 and H10 wherein the hemagglutinin protein is derived from a strain of Influenza A virus, wherein the RNA polynucleotide includes a chemical modification and a pharmaceutically acceptable carrier or excipient, formulated within a lipid nanoparticle, wherein the lipid nanoparticle has about 20-60 mol % ionizable cationic lipid; about 5-25 mol % non-cationic lipid; about 25-55 mol % sterol; and about 0.5-15 mol % PEG-modified lipid.
24. The nucleic acid immunogenic composition of claim 23 , wherein the hemagglutinin protein does not comprise the head domain (HA1).
25. The nucleic acid immunogenic composition of claim 23 , wherein the hemagglutinin protein does not comprise the cytoplasmic domain.
26. The nucleic acid immunogenic composition of claim 23 , wherein the hemagglutinin protein does not comprise the transmembrane domain.