Zika virus vaccines

1. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a human secretory signal peptide hidden Markov model, wherein the human secretory signal peptide hidden Markov model comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2; and

the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.

2. The immunogen of claim 1 , wherein the human secretory signal peptide hidden Markov model comprises the amino acid sequence of SEQ ID NO: 2.

3. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is an IgG signal peptide, wherein:

a) the IgG signal peptide is a mouse IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3; or

b) the IgG signal peptide is a human IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 4,

and wherein

c) the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.

4. The immunogen of claim 3 , wherein the mouse IgG signal peptide comprises the amino acid sequence of SEQ ID NO: 3.

5. The immunogen of claim 3 , wherein the human IgG signal peptide comprises the amino acid sequence of SEQ ID NO: 4.

6. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a prM signal peptide, wherein the prM signal peptide is a human IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 5 and the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.

7. The immunogen of claim 6 , wherein the prM signal peptide comprises the amino acid sequence of SEQ ID NO: 5.

8. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and

wherein the multimerization domain is an immunoglobulin Fc domain, and wherein the immunoglobulin Fc domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9, and wherein the immunoglobulin Fc domain forms a dimer in vivo.

9. The immunogen of claim 8 , wherein the immunoglobulin Fc domain comprises the amino acid sequence of SEQ ID NO: 9.

10. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and

wherein the multimerization domain is a T4 fibritin foldon trimerization domain, and wherein the T4 fibritin foldon trimerization domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 10, wherein the fibritin foldon trimerization domain forms a trimer in vivo.

11. The immunogen of claim 10 , wherein the T4 fibritin foldon trimerization domain comprises the amino acid sequence of SEQ ID NO: 10.

12. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and

wherein the multimerization domain is the a human collagen XV trimerization domain, and wherein the human collagen XV trimerization domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 11, wherein the human collagen XV trimerization domain forms a trimer in vivo.

13. The immunogen of claim 12 , wherein the human collagen XV trimerization domain comprises the amino acid sequence of SEQ ID NO: 11.

14. An immunogen comprising a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, a multimerization domain, and a premembrane (prM) of ZIKV wherein:

the signal peptide is a prM signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and

the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain

and the prM of ZIKV comprises an amino acid sequence at least 95% identical to SEQ ID NO: 8.

15. The immunogen of claim 14 , wherein the prM of ZIKV comprises the amino acid sequence of SEQ ID NO: 8.

16. A dissolvable microneedle array for transdermal insertion into a subject

for promoting an immune response against Zika virus (ZIKV) in a subject in need thereof, the array comprising:

a base portion; and

a plurality of microneedles extending from the base portion and containing an immunogen, and optionally at least one adjuvant, wherein the immunogen comprises a fusion protein, wherein the fusion protein comprises a Zika virus (ZIKV) envelope protein, a signal peptide, and a multimerization domain, wherein:

the signal peptide is a premembrane (prM) signal peptide, an IgG signal peptide, or a human secretory signal peptide hidden Markov model, and

the multimerization domain is an immunoglobulin Fc domain, a T4 fibritin foldon trimerization domain, or a human collagen XV trimerization domain.

17. The dissolvable microneedle array of claim 16 , wherein the each microneedle in the plurality of microneedles are pre-formed to have a shape that comprises a first cross-sectional dimension at a top portion, a second cross-sectional dimension at a bottom portion, and a third cross-sectional dimension at an intermediate portion, wherein the intermediate portion is located between the top portion and the bottom portion, and the third cross-sectional dimension is greater than the first and second cross-sectional dimensions.

18. The dissolvable microneedle array of claim 16 , wherein each microneedle in the plurality of microneedles comprises a plurality of layers of dissoluble biocompatible material.

19. The dissolvable microneedle array of claim 18 , wherein the dissoluble biocompatible material is carboxymethylcellulose.

20. A method of eliciting an immune response against Zika virus (ZIKV) in a subject, comprising contacting the skin of the subject with the microneedle array of claim 16 , thereby delivering the immunogen to the skin of the subject and eliciting the immune response against ZIKV.

21. The method of claim 20 , wherein the subject is a human.

22. The method of claim 21 , wherein the subject is a female.

23. The method of claim 22 , wherein the female is of an age wherein she can bear children.

24. The method of claim 23 , wherein the female is pregnant.

25. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein the signal peptide is the human secretory signal peptide hidden Markov model, and wherein the human secretory signal peptide hidden Markov model comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2.

26. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein the signal peptide is the IgG signal peptide, and wherein:

a) the IgG signal peptide is a mouse IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 3; or

b) the IgG signal peptide is a human IgG signal peptide comprising an amino acid sequence at least 95% identical to SEQ ID NO: 4.

27. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein the signal peptide is the prM signal peptide, and wherein the prM signal peptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 5.

28. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein the multimerization domain is the immunoglobulin Fc domain, and wherein the immunoglobulin Fc domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9, and wherein the immunoglobulin Fc domain forms a dimer in vivo.

29. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein the multimerization domain is the human collagen XV trimerization domain, and wherein the human collagen XV trimerization domain comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 11, wherein the human collagen XV trimerization domain forms a trimer in vivo.

30. The dissolvable microneedle array for transdermal insertion of claim 16 , wherein prM comprises an amino acid sequence at least 95% identical to SEQ ID NO: 8.

31. A nucleic acid molecule encoding the immunogen of claim 1 .

32. A vector comprising the nucleic acid molecule of claim 31 .

33. The vector of claim 32 , wherein the vector is an adenoviral vector.

34. An immunogenic composition comprising the immunogen of claim 1 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

35. The immunogenic composition of claim 34 , further comprising one or more adjuvants.

36. A nucleic acid molecule encoding the immunogen of claim 3 .

37. A vector comprising the nucleic acid molecule of claim 36 .

38. The vector of claim 37 , wherein the vector is an adenoviral vector.

39. An immunogenic composition comprising the immunogen of claim 3 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

40. The immunogenic composition of claim 39 , further comprising one or more adjuvants.

41. A nucleic acid molecule encoding the immunogen of claim 6 .

42. A vector comprising the nucleic acid molecule of claim 41 .

43. The vector of claim 42 , wherein the vector is an adenoviral vector.

44. An immunogenic composition comprising the immunogen of claim 6 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

45. The immunogenic composition of claim 44 , further comprising one or more adjuvants.

46. A nucleic acid molecule encoding the immunogen of claim 10 .

47. A vector comprising the nucleic acid molecule of claim 46 .

48. The vector of claim 47 , wherein the vector is an adenoviral vector.

49. An immunogenic composition comprising the immunogen of claim 10 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

50. The immunogenic composition of claim 49 , further comprising one or more adjuvants.

51. A nucleic acid molecule encoding the immunogen of claim 12 .

52. A vector comprising the nucleic acid molecule of claim 51 .

53. The vector of claim 52 , wherein the vector is an adenoviral vector.

54. An immunogenic composition comprising the immunogen of claim 12 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

55. The immunogenic composition of claim 54 , further comprising one or more adjuvants.

56. A nucleic acid molecule encoding the immunogen of claim 14 .

57. A vector comprising the nucleic acid molecule of claim 56 .

58. The vector of claim 57 , wherein the vector is an adenoviral vector.

59. An immunogenic composition comprising the immunogen of claim 14 , or a vector encoding the immunogen, and a pharmaceutically acceptable carrier.

60. The immunogenic composition of claim 59 , further comprising one or more adjuvants.

61. The immunogen of claim 1 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

62. The immunogen of claim 61 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

63. The immunogen of claim 3 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

64. The immunogen of claim 63 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

65. The immunogen of claim 6 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

66. The immunogen of claim 65 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

67. The immunogen of claim 10 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

68. The immunogen of claim 67 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

69. The immunogen of claim 12 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

70. The immunogen of claim 69 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

71. The immunogen of claim 14 , wherein the ZIKV envelope protein comprises an amino acid sequence at least 95% identical to SEQ ID NO: 6 or SEQ ID NO: 7.

72. The immunogen of claim 71 , wherein the ZIKV envelope protein comprises the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.