Vaccines against herpes simplex virus type 2: compositions and methods for eliciting an immune response
Herpes Simplex Virus-2 (HSV-2) infection is a major health concern. The present disclosure provides, inter alia, certain highly effective vaccines and immunogenic compositions against HSV-2. The antigens can be used therapeutically or prophylactically.
1. An immunogenic composition comprising a pharmaceutically-acceptable carrier, an immunostimulatory amount of an adjuvant and a polypeptide comprising:
(a) an amino acid sequence having at least 90% identity to SEQ ID NO:2 wherein the polypeptide does not comprise a full length ICP4 polypeptide;
(b) an amino acid sequence having at least 90% identity to SEQ ID NO:2 and lacking 1-20 amino acids from the N-terminus, C-terminus, or both; or
(c) an amino acid sequence of SEQ ID NO:2 lacking 1-20 amino acids from the N-terminus, C-terminus, or both.
2. The immunogenic composition of claim 1 , further comprising an HSV gD2 polypeptide.
3. The immunogenic composition of claim 1 , further comprising an HSV gD2 polypeptide lacking a transmembrane domain.
4. The immunogenic composition of claim 1 , further comprising an HSV gD2 polypeptide lacking a transmembrane domain and lacking a cytoplasmic domain.
5. The immunogenic composition of claim 1 , further comprising a second polypeptide consisting of the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:4 or SEQ ID NO:5.
6. The immunogenic composition of claim 1 , further comprising a second polypeptide consisting of the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:5.
7. The immunogenic composition of claim 1 , further comprising a second polypeptide consisting of the amino acid sequence of SEQ ID NO: 4.
8. The immunogenic composition of claim 1 , further comprising a second polypeptide consisting of the amino acid sequence of SEQ ID NO:3, and a third polypeptide consisting of the amino acid sequence of SEQ ID NO:4.
9. The immunogenic composition of claim 1 , further comprising a second polypeptide consisting of the amino acid sequence of SEQ ID NO:3, and a third polypeptide consisting of the amino acid sequence of SEQ ID NO:5.
10. An immunogenic composition comprising a pharmaceutically-acceptable carrier, an immunostimulatory amount of an adjuvant and a polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:2, and wherein the polypeptide does not comprise a full length ICP4 polypeptide.
11. An immunogenic composition comprising a pharmaceutically acceptable carrier, an immunostimulatory amount of an adjuvant and a polypeptide comprising an amino acid sequence having at least 90% identity to SEQ ID NO:2 conjugated to an immunogenic carrier, a signal sequence, or a peptide of no more than 20 amino acids at the N-terminus or C-terminus of the polypeptide, and wherein the polypeptide does not comprise a full length ICP4 polypeptide.
12. The immunogenic composition of claim 1 , wherein the polypeptide of (b) or (c) comprises the amino acid sequence of SEQ ID NO:2 lacking 1-10 amino acid residues from the N-terminus, C-terminus, or both.
13. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:5 lacking all or at least 8 contiguous amino acid residues of residues 340-363 of SEQ ID NO:5.
14. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:4 or the amino acid sequence of SEQ ID NO:4 lacking 1-20 amino acids from the N-terminus, C-terminus, or both.
15. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising an amino acid sequence having at least 80% identity to SEQ ID NO:4.
16. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:5 or the amino acid sequence of SEQ ID NO:5 lacking 1-20 amino acids from the N-terminus, C-terminus, or both.
17. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising an amino acid sequence having at least 80% identity to SEQ ID NO:5.
18. The immunogenic composition of claim 7 or 14 , wherein at least one polypeptide is unglycosylated.
19. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising the amino acid sequence of SEQ ID NO:3 or the amino acid sequence of SEQ ID NO:3 lacking 1-20 amino acid residues from the N-terminus, C-terminus, or both.
20. The immunogenic composition of claim 1 , further comprising a second polypeptide comprising an amino acid sequence having at least 85% identity to SEQ ID NO:3.
21. The immunogenic composition of claim 7 or 14 , wherein at least one polypeptide is conjugated to an immunogenic carrier.
22. The immunogenic composition of claim 1 , wherein the adjuvant is one or more purified fractions of quillaja saponins.
23. The immunogenic composition of claim 22 , wherein the adjuvant comprises saponin fraction A and saponin fraction C.
24. The immunogenic composition of claim 23 , wherein the adjuvant comprises cholesterol, phosphatidyl choline, saponin fraction A and saponin fraction C.
25. The immunogenic composition of claim 24 , wherein the adjuvant is in the form of particles.
26. The immunogenic composition of claim 25 , wherein particles comprising saponin fraction A are substantially free of saponin fraction C and particles comprising saponin fraction C are substantially free of saponin fraction A.
27. The immunogenic composition of claim 1 , wherein the immunogenic composition comprises 5-200 μg of the polypeptide and 5-200 μg of the adjuvant.
28. The immunogenic composition of claim 7 or 14 , wherein at least one polypeptide is conjugated to a tag.
29. The immunogenic composition of claim 1 , wherein upon administration to a subject, the immunogenic composition inhibits infection by HSV-1, HSV-2, or HSV-1 and HSV-2 in the subject.
30. The immunogenic composition of claim 1 , wherein upon administration to a subject, the immunogenic composition treats infection by HSV-2 in the subject.
31. The immunogenic composition of claim 1 , wherein upon administration to a subject infected with HSV-2, the immunogenic composition treats herpes in the subject.
32. The immunogenic composition of claim 31 , wherein the herpes is genital herpes.
33. The immunogenic composition of claim 1 , wherein the immunogenic composition inhibits herpes symptoms in a subject infected with HSV-2.
34. The immunogenic composition of claim 1 , wherein the immunogenic composition inhibits onset of herpes symptoms in a subject infected with HSV-2.
35. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces severity of herpes symptoms in a subject infected with HSV-2.
36. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces recurrence of outbreaks in a subject infected with HSV-2.
37. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces the severity of herpetic lesions in a subject infected with HSV-2.
38. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces the number of days a subject experiences herpetic lesions in a subject infected with HSV-2.
39. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces the frequency of herpes symptoms in a subject infected with HSV-2.
40. The immunogenic composition of claim 1 , wherein the immunogenic composition reduces viral shedding in a subject infected with HSV-2.
41. The immunogenic composition of claim 40 , wherein the immunogenic composition reduces viral transmission in a subject infected with HSV-2.
42. The immunogenic composition of claim 1 , wherein the immunogenic composition increases the IgG titer to one or more HSV-2 antigens in a subject infected with HSV-2.
43. The immunogenic composition of claim 1 , wherein the immunogenic composition activates the T cell response to one or more HSV-2 antigens in a subject infected with HSV-2.
44. The immunogenic composition of claim 1 , wherein the immunogenic composition increases the T cell response to one or more HSV-2 antigens in a subject infected with HSV-2.
45. The immunogenic composition of claim 30 , wherein the immunogenic composition treats infection by HSV-2 in three or fewer doses.
46. A method of treating a subject suffering from or susceptible to HSV-2 infection, comprising administering to the subject an effective amount of the immunogenic composition according to claim 1 , thereby treating the subject.
47. The method of claim 46 , wherein administering the immunogenic composition treats infection by HSV-2 in the subject.
48. The method of claim 46 , wherein administering the immunogenic composition treats herpes in the subject.
49. The method of claim 48 , wherein the herpes is genital herpes.
50. The method of claim 46 , wherein administering the immunogenic composition inhibits herpes symptoms.
51. The method of claim 46 , wherein administering the immunogenic composition inhibits onset of herpes symptoms.
52. The method of claim 46 , wherein administering the immunogenic composition reduces severity of herpes symptoms.
53. The method of claim 46 , wherein administering the immunogenic composition reduces recurrence of outbreaks in a subject infected with HSV-2.
54. The method of claim 46 , wherein administering the immunogenic composition reduces the severity of herpetic lesions.
55. The method of claim 46 , wherein administering the immunogenic composition reduces the number of days a subject experiences herpetic lesions.
56. The method of claim 46 , wherein the immunogenic composition reduces the frequency of herpes symptoms.
57. The method of claim 46 , wherein administering the immunogenic composition reduces viral shedding.
58. The method of claim 57 , wherein administering the immunogenic composition reduces viral transmission.
59. The method of claim 46 , wherein administering the immunogenic composition inhibits infection by HSV-2 in an uninfected subject.
60. The method of claim 46 , wherein administering the immunogenic composition increases the IgG titer to one or more HSV-2 antigens.
61. The method of claim 46 , wherein administering the immunogenic composition activates the T cell response to one or more HSV-2 antigens.
62. The method of claim 46 , wherein administering the immunogenic composition increases the T cell response to one or more HSV-2 antigens.
63. The method of claim 46 , wherein administering the immunogenic composition treats a subject within a three dose regimen.
64. The method of claim 46 , wherein administration of the immunogenic composition occurs prior to, concurrent with, or subsequent to treatment with an antiviral molecule.
65. The method of claim 46 , wherein the subject is a human.
66. The immunogenic composition of claim 1 , wherein the immunogenic composition inhibits re-activation of the virus in a subject infected with HSV-2.
67. The method of claim 46 , wherein administering the immunogenic composition inhibits re-activation of the virus.
68. The immunogenic composition of claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO:2, or consists of an amino acid sequence of SEQ ID NO:2 lacking 1-20 amino acids from the N-terminus, C-terminus, or both.
69. A method of inhibiting infection by HSV-1, HSV-2, or HSV-1 and HSV-2 in a subject, comprising administering to the subject an effective amount of the immunogenic composition according to claim 1 , thereby inhibiting infection.