Infectious disease vaccines
Aspects of the disclosure relate to nucleic acid vaccines. The vaccines include one or more RNA polynucleotides having an open reading frame encoding one or more Chikungunya antigen(s), one or more Zika virus antigens, and one or more Dengue antigens. Methods for preparing and using such vaccines are also described.
1. A method of inducing in a subject an immune response to Zika virus (ZIKV), the method comprising: administering to the subject a composition comprising a messenger ribonucleic acid (mRNA) polynucleotide having an open reading frame encoding a ZIKV antigenic polypeptide formulated in a lipid nanoparticle, wherein the composition is administered in an amount effective to produce an immune response specific to ZIKV.
2. The method of claim 1 , wherein the subject is administered a single dose of the composition.
3. The method of claim 1 , wherein the subject is administered a booster dose of the composition.
4. The method of claim 1 , wherein the composition is administered to the subject by intradermal injection or intramuscular injection.
5. The method of claim 1 , wherein the effective amount is a total dose of 50 μg-1000 μg.
6. The method of claim 1 , wherein the antigenic polypeptide is selected from the group consisting of a ZIKV capsid protein, a ZIKV premembrane/membrane protein, a ZIKV envelope protein, a ZIKV non-structural protein 1, a ZIKV non-structural protein 2A, a ZIKV non-structural protein 2B, a ZIKV non-structural protein 3, a ZIKV non-structural protein 4A, a ZIKV non-structural protein 4B, and a ZIKV non-structural protein 5.
7. The method of claim 1 , wherein the lipid nanoparticle is a cationic lipid nanoparticle.
8. The method of claim 7 , wherein the cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid.
9. The method of claim 8 , wherein the cationic lipid nanoparticle comprises a molar ratio of about 20-60% cationic lipid, 0.5-15% PEG-modified lipid, 25-55% sterol, and 5-25% non-cationic lipid.
10. The method of claim 8 , wherein the cationic lipid is an ionizable cationic lipid, the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
11. The method of claim 1 , wherein the mRNA polynucleotide comprises a chemical modification.
12. The method of claim 11 , wherein the chemical modification is in the carbon 5-position of the uracil.
13. The method of claim 11 , wherein the chemical modification is selected from pseudouridine, 1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 5-methyluridine, 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.
14. The method of claim 13 , wherein the chemical modification is a 1-methylpseudouridine.
15. The method of claim 11 , wherein at least 80% of the uracil in the open reading frame have a chemical modification.
16. The method of claim 15 , wherein 100% of the uracil in the open reading frame have a chemical modification.
17. The method of claim 6 , wherein the antigenic polypeptide is a ZIKV prME protein.
18. The method of claim 1 , wherein the antigenic polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 76-134.
19. A method of inducing in an subject an immune response to Zika virus (ZIKV), the method comprising: administering to the subject a composition comprising a ribonucleic acid (RNA) polynucleotide having an open reading frame encoding a ZIKV antigenic polypeptide, a 5′ terminal cap, and a chemical modification, wherein the RNA polynucleotide is formulated in a lipid nanoparticle, and wherein the composition is administered in an amount effective to produce an immune response specific to ZIKV.