Respiratory virus nucleic acid vaccines
Provided herein, in some embodiments, are vaccines (and vaccination methods) that include a ribonucleic acid (RNA) polynucleotide encoding a human metapneumovirus (hMPV) F protein and a RNA polynucleotide encoding a human parainfluenza virus 3 (hPrV3) F protein.
1. A composition comprising:
a human metapneumovirus (hMPV) messenger ribonucleic acid (mRNA) comprising a 5′ UTR that comprises the sequence of SEQ ID NO:12, an open reading frame that comprises the sequence of SEQ ID NO:4, and a 3′ UTR that comprises the sequence of SEQ ID NO:13; and
a human parainfluenza virus 3 (hPIV3) mRNA comprising a 5′ UTR that comprises the sequence of SEQ ID NO:12, an open reading frame that comprises the sequence of SEQ ID NO:5, and a 3′ UTR that comprises the sequence of SEQ ID NO:13.
2. The composition of claim 1 , wherein the hMPV mRNA comprises the sequence of SEQ ID NO: 14.
3. The composition of claim 1 , wherein the hPIV3 mRNA comprises the sequence of SEQ ID NO: 15.
4. The composition of claim 1 comprising the hMPV mRNA and the hPIV3 mRNA at a mass ratio of 1:1.
5. The composition of claim 1 , wherein the hMPV mRNA comprises a 7mG(5′)ppp(5′)NlmpNp cap and/or the hPIV3 mRNA comprises a 7mG(5′)ppp(5′)NlmpNp cap.
6. The composition of claim 1 , wherein the hMPV mRNA comprises a polyA tail and/or the hPIV3 mRNA comprises a polyA tail.
7. The composition of claim 1 , wherein the hMPV mRNA and/or the hPIV3 mRNA comprises a chemical modification.
8. The composition of claim 7 , wherein the chemical modification is 1-methylpseudouridine.
9. The composition of claim 1 comprising 25 μg 200 μg of the hMPV mRNA.
10. The composition of claim 1 comprising 25 μg 200 μg of the hPIV3 mRNA.
11. The composition of claim 1 further comprising mRNA encoding a respiratory syncytial virus (RSV) antigen.
12. The composition of claim 1 , wherein the hMPV mRNA and the hPIV3 mRNA are in a lipid nanoparticle that comprises 1-5 mol % PEG-modified lipid; 10-20 mol % non-cationic lipid; 35-45 mol % cholesterol; and 40-50 mol % ionizable cationic lipid.
13. The composition of claim 12 , wherein the PEG-modified lipid is 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG), the non-cationic lipid is 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC), and the ionizable cationic lipid has the structure of Compound 1:
14. A composition comprising:
25 μg-200 μg human metapneumovirus (hMPV) messenger ribonucleic acid (mRNA) comprising the sequence of SEQ ID NO:14; and
25 μg-200 μg a human parainfluenza virus 3 (hPIV3) mRNA comprising the sequence of SEQ ID NO:15.
15. The composition of claim 14 , wherein the hMPV mRNA and the hPIV3 mRNA are in a lipid nanoparticle that comprises 1-5 mol % 1,2 dimyristoyl-sn-glycerol, methoxypolyethyleneglycol (PEG2000 DMG); 10-20 mol % 1,2 distearoyl-sn-glycero-3-phosphocholine (DSPC); 35-45 mol % cholesterol; and 40-50 mol % ionizable cationic lipid having the structure of Compound 1:
16. The composition of claim 14 further comprising mRNA encoding a respiratory syncytial virus (RSV) antigen.
17. A method comprising administering to a subject the composition of claim 12 in an amount effective to induce a neutralizing antibody response against hMPV and/or hPIV3 in the subject.
18. The method of claim 17 , wherein the subject is immunocompromised and/or has a pulmonary disease.
19. The method of claim 17 , wherein the subject is 5 years of age or younger, or 65 years of age or older.
20. The method of claim 17 comprising administering to the subject at least two doses of the composition.
21. The method of claim 20 , wherein a neutralizing antibody titer against hMPV in the subject at 14 days post-administration of the second dose of the composition is increased by 8-10 fold relative to a control, and/or a neutralizing antibody titer against hPIV3 in the subject at 14 days post-administration of the second dose of the composition is increased by 4-10 fold relative to a control.
22. The composition of claim 12 , wherein the lipid nanoparticle comprises 2.5 mol % PEG2000 DMG, 10 mol % DSPC, 38.5 mol % cholesterol; and 49 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
23. The composition of claim 12 , wherein the lipid nanoparticle comprises 2.5 mol % PEG2000 DMG, 11 mol % DSPC, 38.5 mol % cholesterol; and 48 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
24. The composition of claim 12 , wherein the lipid nanoparticle comprises 3.5 mol % PEG2000 DMG, 11 mol % DSPC, 38.5 mol % cholesterol; and 49 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
25. The composition of claim 15 , wherein the lipid nanoparticle comprises 2.5 mol % PEG2000 DMG, 10 mol % DSPC, 38.5 mol % cholesterol; and 49 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
26. The composition of claim 15 , wherein the lipid nanoparticle comprises 2.5 mol % PEG2000 DMG, 11 mol % DSPC, 38.5 mol % cholesterol; and 48 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
27. The composition of claim 15 , wherein the lipid nanoparticle comprises 3.5 mol % PEG2000 DMG, 11 mol % DSPC, 38.5 mol % cholesterol; and 49 mol % ionizable cationic lipid, and wherein the ionizable lipid has the structure of Compound 1:
28. The composition of claim 8 , wherein 100% of uracil in the open reading frame of the hMPV mRNA and open reading frame of the hPIV3 mRNA comprise a 1-methylpseudouridine.