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1. WO2013006569 - HERPES VIRUS VACCINE AND METHODS OF USE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

WHAT IS CLAIMED IS:

1. A Herpesvirus (HV) vaccine comprising inactivated HV, a lipopolysaccharide (LPS)-derived adjuvant and an aluminum-based mineral salt adjuvant.

2. The vaccine of claim 1,

wherein said LPS-derived adjuvant is MPL;

said aluminum-based mineral salt adjuvant is aluminum hydroxide adjuvant or aluminum phosphate adjuvant; and

said vaccine does not comprise an isolated nucleic acid sequence formulation.

3. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-3.

4. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-4.

5. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-5.

6. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-6.

7. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-7.

8. The vaccine of any one of claims 1 to 2, wherein said HV is HHV-8.

9. The vaccine of any one of claims 1 to 2, wherein said HV is a Herpes Simplex Virus (HSV).

10. The vaccine of claim 1, wherein said HV is HSV1.

1 1. The vaccine of claim 1, wherein said HV is HSV2.

12. The vaccine of claim 1, wherein said HV is HSV1 and HSV2.

13. The vaccine of claim 9, wherein said lipopolysaccharide-derived adjuvant is derived from the Salmonella Minnesota LPS.

14. The vaccine of claim 9, wherein said lipopolysaccharide-derived adjuvant s derived from the Salmonella minnesota Re595 LPS.

15. The vaccine of claim 9, wherein said lipopolysaccharide-derived adjuvant s derived from the R595 LPS.

16. The vaccine of claim 12, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant.

17. The vaccine of claim 12, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant without an (R)-3-hydroxytetradecanoyl moiety.

18. The vaccine of claim 9, wherein said lipopolysaccharide-derived adjuvant is monophosphoryl lipid A (MPL)

19. The vaccine of claim 12, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant without a 1-phosphate moiety.

20. The vaccine claim 12, wherein said lipopolysaccharide-derived adjuvant is 3 -O-desacyl-4' -monophosphoryl lipid A.

21. The vaccine of claim 9, wherein said lipopolysaccharide-derived adjuvant is capable of binding the TLR4 protein.

22. The vaccine of claim 12, wherein said lipopolysaccharide-derived adjuvant is a synthetic MPL analogue adjuvant.

23. The vaccine of claim 9, wherein said aluminum-based mineral salt adjuvant is aluminum hydroxide adjuvant.

24. The vaccine of claim 9, wherein said aluminum-based mineral salt adjuvant is aluminum phosphate adjuvant.

25. The vaccine of claim 12, wherein said aluminum -based mineral salt adjuvant is a potassium aluminum sulfate adjuvant.

26.. The vaccine of claim 9, wherein said aluminum -based mineral salt adjuvant includes crystalline aluminum hydroxide and not amorphous aluminum hydroxide or aluminum hydroxycarbonate or magnesium hydroxide.

27. The vaccine of claim 9, wherein said aluminum-based mineral salt adjuvant includes aluminum phosphate gel in the form of a white gelatinous precipitate.

28. The vaccine of claim 9, wherein said aluminum -based mineral salt adjuvant includes aluminum hydroxide gel in the form of a white gelatinous precipitate.

29. The vaccine of claim 9, wherein said inactivated HV comprises a replication decreasing DNA mutation.

30. The vaccine of claim 9, wherein said inactivated HV is formed by chemical inactivation.

31. The vaccine of claim 9, wherein said inactivated HV is formed by contacting said HV with one or more agents selected from a cross-linking agent, oxidizing agent, reducing agent, heat, radiation, detergent, a pH changing agent, and a chemical agent selected from a furocoumarin, aziridine, ethylenimine, binary ethylenimine, and beta-propiolactone.

32. The vaccine of claim 31, wherein said chemical agent is aziridine.

33. The vaccine of claim 31, wherein said chemical agent is ethylenimine.

34. The vaccine of claim 31, wherein said chemical agent is binary ethylenimine.

35. The vaccine of claim 31, wherein said chemical agent is beta-propiolactone.

36. The vaccine of claim 31, wherein said radiation is UV radiation.

37. The vaccine of claim 31, wherein said radiation is electron beam radiation.

38. The vaccine of claim 31, wherein said radiation is infrared radiation.

39. The vaccine of claim 31, wherein said radiation is gamma radiation.

40. The vaccine of claim 31, wherein said cross-linking agent is an aldehyde cross-linking agent.

41. The vaccine of claim 31, wherein said cross-linking agent is formaldehyde.

42. The vaccine of claim 31, wherein said cross-linking agent is formalin.

43. The vaccine of claim 31, wherein said oxidizing agent is sodium periodate.

44 . The vaccine of claim 31, wherein said oxidizing agent is hydrogen peroxide.

45. The vaccine of claim 31, wherein said reducing agent is aldrithiol-2.

46. The vaccine of claim 31, wherein said detergent is Triton-X-100.

47. The vaccine of claim 31, wherein said detergent is NP-40.

48. The vaccine of claim 31 , wherein said detergent is Tween-20.

49. The vaccine of claim 9, wherein said inactivated HV is formed by contacting said HV with one or more agents comprising UV radiation and a furocoumarin.

50. The vaccine of claim 49, wherein said furocoumarin is psoralen.

51. The vaccine of claim 49, wherein said furocoumarin is 4'-aminomethyl-4,5',8-trimethylpsoralen.

52. The vaccine of claim 49, wherein said furocoumarin is angelicin.

53. The vaccine of claim 49, wherein said furocoumarin is xanthotoxin.

54. The vaccine of claim 49, wherein said furocoumarin is bergapten.

55. The vaccine of any one of claims 31 to 49, wherein said furocoumarin is nodakenetin.

56. The vaccine of claim 9, wherein said inactivated HV is an inactivated single strain of the HV.

57. The vaccine of claim 9, wherein said inactivated HV is a combination of two or more inactivated strains of the HV.

58. The vaccine of claim 56, wherein said inactivated HV is an inactivated single strain of the HSV1.

59. The vaccine of claim 56, wherein said inactivated HV is an inactivated single strain of HSV2.

60. The vaccine of claim 57, wherein said inactivated HV is a combination of two or more inactivated strains of HS V 1.

61. The vaccine of claim 57, wherein said inactivated HV is a combination of two or more inactivated strains of HSV2.

62. The vaccine of claim 9, wherein said inactivated HV is a combination of one or more inactivated strains or HSVl and one or more inactivated strains of HSV2.

63. The vaccine of claim 9, formulated for intramuscular administration.

64. The vaccine of claim 9, formulated for intradermal administration.

65. The vaccine of claim 9, formulated for mucosal administration.

66. The vaccine of claim 9, formulated for intranasal administration.

67. The vaccine of claim 9, formulated for intrarectal administration.

68. The vaccine of claim 9, formulated for intravaginal administration.

69. The vaccine of claim 9, formulated for topical administration.

70. The vaccine of claim 9, formulated for transcutaneous administration.

71. The vaccine of claim 9, formulated for subcutaneous administration.

72. The vaccine of claim 2, wherein said isolated nucleic acid sequence formulation is an antigenic isolated nucleic acid sequence formulation.

73. The HV vaccine of claim 2, wherein said isolated nucleic acid sequence formulation is a DNA vaccine.

74. The HV vaccine of claim 73, wherein said DNA vaccine is an antigenic isolated nucleic acid sequence formulation.

75. The HV vaccine of claim 9, wherein said vaccine vaccinates a recipient of said vaccine against HV infection for up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more years.

76. A method of preparing a Herpesvirus (HV) vaccine, said method comprising:

(i) contacting an HV -cell mixture with a sulfated or sulfonated polysaccharide, wherein said HV -cell mixture comprises HV particles, cells and portions of cells;

(ii) separating said HV particles from said cells thereby forming isolated HV particles;

(iii) inactivating said isolated HV particles thereby forming inactivated HV particles;

(iv) combining said inactivated HV particles with a lipopolysaccharide-derived adjuvant and an aluminum-based mineral salt adjuvant thereby forming an HV vaccine.

77. The method of claim 76, wherein said HV is an HSV.

78. The method of claim 77, wherein said HSV is HSV1.

79. The method of claim 77, wherein said HSV is HSV2.

80. The method of claim 77, wherein said HSV is HSV1 and HSV2.

81. The method of claim 77, wherein said sulfated or sulfonated polysaccharide is selected from dextran sulfate, heparin, and heparan sulfate.

82. The method of claim 77, wherein said HV particles are isolated at a concentration of 107 to 1010 (pfu/microgram protein).

83. The method of claim 77, wherein said HV vaccine comprises 107 to 1010 (pfu equivalents/microgram protein) of inactivated HV.

84. The method of claim 77, wherein said separating comprises centrifugation, polyethylene glycol precipitation, filtration, gel filtration, ultra-filtration, tangential flow ultra-filtration, or affinity chromatography.

85. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is derived from the Salmonella Minnesota LPS.

86. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is derived from the Salmonella minnesota Re595 LPS.

87. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is derived from the R595 LPS.

88. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant.

89. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant without a (R)-3-hydroxytetradecanoyl moiety.

90. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is monophosphoryl lipid A (MPL).

91. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is a lipid A adjuvant without a 1 -phosphate moiety.

92. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is 3 -O-desacyl-4' -monophosphoryl lipid A.

93. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is a synthetic MPL analogue adjuvant.

94. The method of claim 77, wherein said lipopolysaccharide-derived adjuvant is capable of binding the TLR4 protein.

95. The method of claim 77, wherein said aluminum-based mineral salt adjuvant is an aluminum hydroxide adjuvant.

96. The method of claim 77, wherein said aluminum-based mineral salt adjuvant is an aluminum phosphate adjuvant.

97. The method of claim 77, wherein said aluminum-based mineral salt adjuvant includes crystalline aluminum hydroxide and not amorphous aluminum hydroxide or aluminum hydroxycarbonate or magnesium hydroxide.

98. The method of claim 77, wherein said aluminum-based mineral salt adjuvant includes aluminum phosphate gel in the form of a white gelatinous precipitate.

99. The method of claim 77, wherein said aluminum-based mineral salt adjuvant includes aluminum hydroxide gel in the form of a white gelatinous precipitate.

100. The method of claim 77, wherein said aluminum-based mineral salt adjuvant is a potassium aluminum sulfate adjuvant.

101. The method of claim 77, wherein said inactivating comprises contacting said HV with one or more agents selected from a cross-linking agent, oxidizing agent, reducing agent, heat, radiation, detergent, a pH changing agent, and a chemical agent selected from a furocoumarin, aziridine, ethylenimine, binary ethylenimine, and beta-propiolactone.

102. The method of claim 101, wherein said chemical agent is aziridine.

103. The method of claim 101, wherein said chemical agent is ethylenimine.

104. The method of claim 101, wherein said chemical agent is binary ethylenimine.

105. The method of claim 101, wherein said chemical agent is beta-propiolactone.

106. The method of claim 101, wherein said radiation is UV radiation.

107. The method of claim 101, wherein said radiation is electron beam radiation.

108. The method of claim 101, wherein said radiation is infrared radiation.

109. The method of claim 101, wherein said radiation is gamma radiation.

1 10. The method of claim 101, wherein said cross-linking agent is an aldehyde cross-linking agent.

1 11. The method of claim 101, wherein said cross-linking agent is formaldehyde.

1 12. The method of claim 101, wherein said cross-linking agent is formalin.

113. The method of claim 101, wherein said oxidizing agent is sodium periodate.

114 . The method of claim 101, wherein said oxidizing agent is hydrogen peroxide.

1 15. The method of claim 101, wherein said reducing agent is aldrithiol-2.

116. The method of claim 101, wherein said detergent is Triton-X-100.

1 17. The method of claim 101 wherein said detergent is NP-40.

118. The method of claim 101, wherein said detergent is Tween-20.

1 19. The method of claim 77, wherein said inactivating comprises contacting said HV with one or more agents comprising UV radiation and a furocoumarin.

120. The method of claim 1 19, wherein said furocoumarin is psoralen.

121. The method of claim 1 19, wherein said furocoumarin is 4'-aminomethyl-4,5', 8-trimethylpsoralen.

122. The method of claim 1 19, wherein said furocoumarin is angelicin.

123. The method of claim 1 19, wherein said furocoumarin is xanthotoxin.

124. The method of claim 1 19, wherein said furocoumarin is bergapten.

125. The method of claim 119, wherein said furocoumarin is nodakenetin.

126. A method of treating or preventing HV infection in a patient in need of such treatment or prevention, said method comprising administering a therapeutically or prophylactically effective amount of the HV vaccine of claim 9.

127. The method of claim 126, wherein said HV is an HSV.

128. The method of claim 127, wherein said HSV is HSV1.

129. The method of claim 127, wherein said HSV is HSV2.

130. The method of claim 127, wherein said HSV is HSV1 and HSV2.

131. The method of claim 127, wherein said HV infection causes a disease selected from herpetic gingivostomatitis, herpes labialis, herpes genitalis, herpetic whitlow, herpes gladiatorum, herpesviral encephalitis, herpesviral meningitis, herpes esophagitis, herpes keratitis, Bell's palsy, Mollaret's meningitis, herpes rugbeiorum, eczema herpeticum, herpetic neuralgia, and post-herpetic neuralgia.

132. A method of treating or preventing a disease in a patient in need of such treatment or prevention, said method comprising administering a therapeutically or

prophylactically effective amount of the HV vaccine of claim 9.

133. The method of claim 132, wherein said disease is an HV associated disease.

134. The method claim 133, wherein said HV is an HSV.

135. The method of claim 134, wherein said HSV is HSV1.

136. The method of claim 134, wherein said HSV is HSV2.

137. The method of claim 134, wherein said HSV is HSV1 and HSV2.

138. The method of claim 134, wherein said disease is selected from the group consisting of herpetic gingivostomatitis, herpes labialis, herpes genitalis, herpetic whitlow, herpes gladiatorum, herpesviral encephalitis, herpesviral meningitis, herpes esophagitis, herpes keratitis, Bell's palsy, Mollaret's meningitis, herpes rugbeiorum, eczema herpeticum, herpetic neuralgia, and post-herpetic neuralgia.

139. The method of claim 138, wherein said disease is herpetic gingivostomatitis.

140. The method of claim 138, wherein said disease is herpes labialis.

141. The method of claim 138, wherein said disease is herpes genitalis.

142. The method of claim 138, wherein said disease is herpetic whitlow.

143. The method of claim 138, wherein said disease is herpes gladiatorum.

144. The method of claim 138, wherein said disease is herpesviral encephalitis.

145. The method of claim 138, wherein said disease is herpesviral meningitis.

146. The method of claim 138, wherein said disease is herpes esophagitis.

147. The method of claim 138, wherein said disease is herpes keratitis.

148. The method of claim 138, wherein said disease is Bell's palsy.

149. The method of claim 138, wherein said disease is Mollaret's meningitis.

150. The method of claim 138, wherein said disease is herpes rugbeiorum.

151. The method of claim 138, wherein said disease is eczema herpeticum.

152. The method of claim 138, wherein said disease is herpetic neuralgia.

153. The method of claim 138, wherein said disease is post-herpetic neuralgia.

154. The method of claim 138, wherein said disease is Alzheimer's disease.

155. The method of claim 138, wherein said method is a method of treating.

156. The method of claim 138, wherein said method is a method of preventing.

157. The method of claim 138, wherein said method includes a therapeutically effective amount of the HSV vaccine.

158. The method of claim 138, wherein said method includes a prophylactically effective amount of the HSV vaccine..

159. The method of claim 138, comprising a reduction in viral shedding.

160. The method of claim 138, comprising a reduction in the frequency of lesion occurrence.

161. The method of claim 138, comprising a reduction in the duration of lesion occurrence.

162. The method of claim 138, comprising intramuscular administration.

163. The method of claim 138, comprising intradermal administration.

164. The method of claim 138, comprising mucosal administration.

165. The method of claim 138, comprising intranasal administration.

166. The method of claim 138, comprising intrarectal administration.

167. The method of claim 138, comprising intravaginal administration.

168. The method of claim 138, comprising topical administration.

169. The method of claim 138, comprising transcutaneous administration.

170. The method of claim 138, comprising subcutaneous administration.

171. The method of claim 134, wherein an isolated nucleic acid sequence formulation is not administered to said patient.

172. The method of claim 171, wherein said isolated nucleic acid sequence formulation is a DNA sequence.

173. The method of claim 171, wherein said isolated nucleic acid sequence formulation is a nucleic acid vaccine.

174. The method of claim 171, wherein said isolated nucleic acid sequence formulation is a DNA vaccine.

175. The method of claim 138, wherein said method does not comprise administration of a prime HSV DNA vaccine.

176. The method of claim 138, wherein said method does not comprise administration of an HSV DNA vaccine.

177. The method of claim 138, wherein said method does not comprise administration of a DNA vaccine comprising a gene selected from HSV UL30, UL5, gD2, gD2t, or portions thereof.

178. The method of claim 138, consisting of a single administration of said HSV vaccine.

179. The method of claim 138, consisting of a prime-boost administration of said HSV vaccine.

180. The method of claim 138, consisting of a prime-boost-boost administration of said HSV vaccine.

181. A kit comprising the HV vaccine of claim 9 and instructions for administering said HV vaccine to a patient.

182. The kit of claim 181, wherein said HV vaccine is administered in a prime-boost administration.