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 corresponding 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, wherein the sequence identity is determined by Needleman-Wunsch homology alignment, 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;
wherein the Zika virus comprises an E protein having an amino acid sequence provided by SEQ ID NO: 47; and
wherein the Zika virus is Vero cell adapted and is able to pack a virulent Zika virus.
2. The Zika virus vaccine of claim 1 , wherein the RNA genome corresponds to the DNA sequence provided by SEQ ID NO: 4.
3. The Zika virus vaccine of claim 1 , wherein the variant nucleic acid has at least 99.5% identity to SEQ ID NO: 4, wherein the sequence identity is determined by Needleman-Wunsch homology alignment.
4. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 20.
5. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 30.
6. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 40.
7. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 50.
8. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 60.
9. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 70.
10. The Zika virus vaccine of claim 1 , wherein said MN50 is greater than 80.
11. The Zika virus vaccine of claim 1 , wherein said MN50 is greater or equal to 90.
12. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 80% of vaccinated subjects.
13. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 90% of vaccinated subjects.
14. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 95% of vaccinated subjects.
15. The Zika virus vaccine of claim 1 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 99% of vaccinated subjects.
16. The Zika virus vaccine of claim 1 , wherein the Zika virus is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation.
17. The Zika virus vaccine of claim 16 , 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.
18. The Zika virus vaccine of claim 16 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde.
19. The Zika virus vaccine of claim 18 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde for between 2-10 days.
20. The Zika virus vaccine of claim 18 , wherein the chemical activation is performed at about +4° C. or about +22° C.
21. The Zika virus vaccine of claim 1 , further comprising an adjuvant.
22. The Zika virus vaccine of claim 21 , wherein the adjuvant is an aluminium salt adjuvant.
23. The Zika virus vaccine of claim 22 , 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.
24. The Zika virus vaccine of claim 21 , wherein the adjuvant comprises a peptide and a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN).
25. The Zika virus vaccine of claim 24 , wherein the peptide comprises the sequence KLKL 5 KLK (SEQ ID NO: 71) and the I-ODN comprises oligo-d(IC) 13 (SEQ ID NO: 70).
26. The Zika virus vaccine of claim 1 , further comprising one or more pharmaceutically acceptable excipients.
27. 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).
28. The Zika virus vaccine of claim 27 , wherein said PS or fragments or break-down products of PS are detectable by mass spectroscopy.
29. 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.
30. The Zika virus vaccine of claim 1 , further comprising a TLR9 agonist.
31. A Zika virus vaccine comprising a Zika virus having an RNA genome corresponding to a DNA sequence having at least 99.9% identity to SEQ ID NO: 4, wherein the sequence identity is determined by Needleman-Wunsch homology alignment, 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;
wherein the Zika virus comprises an E protein having an amino acid sequence provided by SEQ ID NO: 47; and
wherein the Zika virus is Vero cell adapted and is able to pack a virulent Zika virus.
32. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 20.
33. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 30.
34. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 40.
35. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 50.
36. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 60.
37. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 70.
38. The Zika virus vaccine of claim 31 , wherein said MN50 is greater than 80.
39. The Zika virus vaccine of claim 31 , wherein said MN50 is greater or equal to 90.
40. The Zika virus vaccine of claim 31 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 80% of vaccinated subjects.
41. The Zika virus vaccine of claim 31 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 90% of vaccinated subjects.
42. The Zika virus vaccine of claim 31 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 95% of vaccinated subjects.
43. The Zika virus vaccine of claim 31 , wherein the Zika virus vaccine is capable of stimulating a MN50 titer greater than 15 in at least 99% of vaccinated subjects.
44. The Zika virus vaccine of claim 31 , wherein the Zika virus is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation.
45. The Zika virus vaccine of claim 44 , 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.
46. The Zika virus vaccine of claim 44 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde.
47. The Zika virus vaccine of claim 46 , wherein the chemical inactivation comprises contacting the Zika virus with formaldehyde for between 2-10 days.
48. The Zika virus vaccine of claim 46 , wherein the chemical activation is performed at about +4° C. or about +22° C.
49. The Zika virus vaccine of claim 31 , further comprising an adjuvant.
50. The Zika virus vaccine of claim 49 , wherein the adjuvant is an aluminium salt adjuvant.
51. The Zika virus vaccine of claim 50 , 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.
52. The Zika virus vaccine of claim 49 , wherein the adjuvant comprises a peptide and a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN).
53. The Zika virus vaccine of claim 52 , wherein the peptide comprises the sequence KLKL 5 KLK (SEQ ID NO: 71) and the I-ODN comprises oligo-d(IC) 13 (SEQ ID NO: 70).
54. The Zika virus vaccine of claim 31 , further comprising one or more pharmaceutically acceptable excipients.
55. The Zika virus vaccine of claim 31 , 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).
56. The Zika virus vaccine of claim 55 , wherein said PS or fragments or break-down products of PS are detectable by mass spectroscopy.
57. The Zika virus vaccine of claim 31 , 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.
58. The Zika virus vaccine of claim 31 , further comprising a TLR9 agonist.