Zika virus vaccine
Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.
1. A Zika virus vaccine comprising a Zika virus having an RNA genome, wherein said Zika virus vaccine is capable of stimulating a neutralizing antibody titer greater than 15 in at least 70% of vaccinated subjects, wherein the neutralizing antibody titer is determined using a microneutralization assay (MN50) following a single administration of the Zika virus vaccine to a subject; and wherein the Zika virus comprises an E protein having an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 14-69 and is able to pack a virulent Zika virus.
2. The Zika virus vaccine of claim 1 , wherein the Zika virus comprises an E protein having an amino acid sequence having at least 96%, 97%, 98%, 99% or 99.5% sequence identity to any one of SEQ ID NOs: 14-69 and is able to pack a virulent Zika virus.
3. The Zika virus vaccine of claim 1 , wherein the Zika virus comprises an E protein having an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 47 or 48 and is able to pack a virulent Zika virus.
4. The Zika virus vaccine of claim 1 , wherein the Zika virus comprises an E protein having an amino acid sequence having at least 96%, 97%, 98%, 99% or 99.5% sequence identity to SEQ ID NO: 47 or 48 and is able to pack a virulent Zika virus.
5. The Zika virus vaccine of claim 1 , wherein the RNA genome corresponds to the DNA sequence provided by SEQ ID NO: 4 or a variant nucleic acid having at least 99% identity to SEQ ID NO: 4.
6. The Zika virus vaccine of claim 5 , wherein the variant nucleic acid has at least 99.5% identity to SEQ ID NO: 4.
7. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 20.
8. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 30.
9. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 40.
10. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 50.
11. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 60.
12. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 70.
13. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 80.
14. The Zika virus vaccine according to claim 1 , wherein said MN50 is greater than or equal to 90.
15. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating an MN50 titer greater than 15 in at least 80% of vaccinated subjects.
16. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating an MN50 titer greater than 15 in at least 90% of vaccinated subjects.
17. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating an MN50 titer greater than 15 in at least 95% of vaccinated subjects.
18. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating an MN50 titer greater than 15 in at least 99% of vaccinated subjects.
19. The Zika virus vaccine of claim 1 , wherein the Zika virus is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation.
20. The Zika virus vaccine of claim 19 , wherein the chemical inactivation comprises contacting the Zika virus with a chemical inactivation agent for longer than is required to completely inactivate the Zika virus as measured by plaque assay.
21. The Zika virus vaccine of claim 19 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde.
22. The Zika virus vaccine of claim 19 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde for between 2-10 days.
23. The Zika virus vaccine of claim 21 , wherein the chemical activation is performed at about +4° C. or about +22° C.
24. The Zika virus vaccine of claim 1 , further comprising an adjuvant.
25. The Zika virus vaccine of claim 24 , wherein the adjuvant is an aluminium salt adjuvant.
26. The Zika virus vaccine of claim 25 , wherein said aluminium salt adjuvant is aluminium hydroxide with less than 1.25 parts per billion copper based on a final pharmaceutical composition comprising the Zika virus.
27. The Zika virus vaccine of claim 24 , wherein the adjuvant comprises a peptide and a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN).
28. The Zika virus vaccine of claim 27 , wherein the peptide comprises the sequence KLKL5KLK (SEQ ID NO: 71) and the I-ODN comprises oligo-d(IC)13 (SEQ ID NO: 70).
29. The Zika virus vaccine of claim 1 , further comprising one or more pharmaceutically acceptable excipients.
30. The Zika virus vaccine of claim 1 , wherein the vaccine comprises protamine sulphate (PS) or fragments or break-down products of PS at amounts below the limits of detection by high performance liquid chromatography (HPLC).
31. The Zika virus vaccine of claim 30 , wherein said PS or fragments or break-down products of PS are detectable by mass spectroscopy.
32. The Zika virus vaccine of claim 1 , wherein the vaccine comprises protamine sulphate (PS) or fragments or break-down products of PS at amounts below 1 μg/mL or below 100 ng/mL.