Delivery vehicles, bioactive substances and viral vaccines

• US 20060177468A1
• Filed: 01/05/2006
• Published: 08/10/2006
• Est. Priority Date: 01/05/2005
• Status: Abandoned Application

• Current Assignee: Drexel University, Philadelphia Health and Education Corporation, Philadelphia Health Education Corporation
• Original Assignee: (DUCOM), Philadelphia Health and Education Corporation
• Inventors: Boestcanu, Alina, Babu, Nadarajan Sundar, Papazoglou, Elizabeth S., Wheatley, Margaret A., Katsikis, Peter D.
• Application Number:
  US11/327,674
• Publication Number:
  US 20060177468A1
• Time in Patent Office: Days
• US Class Current: 424/209.100
• CPC Class Codes: A61K 2039/5252 inactivated (killed)
• CPC Class Codes: A61K 2039/5254 avirulent or attenuated
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/55511 Organic adjuvants
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/55583 Polysaccharides
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/64 characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/0092 Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C12N 2760/16134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The invention relates to compositions and methods for the safe delivery of a bioactive agent to an animal. Preferably, the bioactive agent is a vaccine, and more preferably, the bioactive agent is a virus.

Claims

1. A vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of virus, wherein said virus induces an immunoprotective CD8+ T cell and/or antibody response in an animal following administration of said virus to said animal by a route that does not cause disease in said animal.

3. The vaccine of claim 1, wherein said virus is a live virus.

4. The vaccine of claim 1, wherein said virus is an attenuated virus.

5. The vaccine of claim 1, wherein said virus is a killed virus.

6. The vaccine of claim 1, wherein said virus is a respiratory virus.

7. The vaccine of claim 1, wherein said virus is selected from the group consisting of an orthomyxovirus, a paramyxovirus, a coronavirus, a picornavirus, respiratory syncytial virus, measles virus, adenovirus, a parvovirus, and adenovirus, a calicivirus, an astrovirus, Norwalk virus, an arenavirus, a flavivirus, a filovirus, a hantavirus, an alphavirus, a retrovirus and a lentivirus.

8. The vaccine of claim 7, wherein said virus is an orthomyxovirus.

9. The vaccine of claim 8, wherein said orthomyxovirus is an influenza virus.

10. The vaccine of claim 9, wherein said influenza virus is influenza virus type A.

11. The vaccine of claim 10, wherein said influenza virus type A has a hemagglutinin antigen (HA) selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 and H16.

12. The vaccine of claim 10, wherein said influenza virus type A has a neuraminidase antigen (NA) selected from the group consisting of N1, N2, N3, N4, N5, N6, N7, N8 and N9.

13. The vaccine of claim 10 wherein said influenza virus type A has a HA:

NA antigenic profile selected from the group consisting of H5N1, H9N2, H7N1, H7N2, H7N3, H7N7, H2N2, H1N1, H1N2 and H3N2.

14. The vaccine of claim 10 comprising a low dose of said influenza virus type A.

15. The vaccine of claim 14, wherein said low dose of influenza type A virus is from 0.001 to 5000 hamagglutination units (HAU) of virus.

16. The vaccine of claim 15, wherein said low dose of influenza virus type A is from 0.005 to 500 HAU of virus.

17. The vaccine of claim 16, wherein said low dose of influenza virus type A is from 0.01 to 100 HAU of virus.

18. The vaccine of claim 1, wherein said animal is a mammal.

19. The vaccine of claim 18, wherein said mammal is a human.

20. The vaccine of claim 1, wherein said virus comprises a combination of two or more of member selected from the group consisting of a live virus, an attenuated virus, and a killed virus.

21. The vaccine of claim 1, wherein said route is a non-natural route.

22. The vaccine of claim 21, wherein said route is selected from the group consisting of subcutaneous, intradermal, intramuscular, mucosal and oral.

23. A kit comprising the vaccine of claim 1.

2. A vaccine comprising a CD8+ T cell immunoprotective amount of virus, wherein said virus induces an immunoprotective CD8+ T cell response in an animal following administration of said virus to said animal by a route that does not cause disease in said animal.

24. A vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of virus, wherein said virus induces an immunoprotective CD8+ T cell and/or antibody response in an animal following administration of said virus to said animal by a route that does not cause disease in said animal, and further wherein said virus is associated with an encapsulation vehicle.

26. The vaccine of claim 24, wherein said virus is encapsulated in said encapsulation vehicle.

27. The vaccine of claim 24 wherein said virus is associated with a nanotube, a lipsome or a protein prior to being encapsulated in said encapsulation vehicle.

28. The vaccine of claim 24, wherein said encapsulation vehicle comprises one or more members selected from the group consisting of a gel, a liquid or a powder.

29. The vaccine of claim 28, wherein said encapsulation vehicle is loaded into a nanotube.

30. The vaccine of claim 24, wherein said encapsulation vehicle comprises a polymer.

31. The vaccine of claim 30, wherein said polymer is not toxic when administered to an animal.

32. The vaccine of claim 30, wherein said polymer is associated with said virus thereby delaying release of said virus into the surrounding environment.

33. The vaccine of claim 30, wherein said polymer is a gel.

34. The vaccine of claim 33, wherein said gel comprises collagen.

35. The vaccine of claim 33, wherein said gel is a hydrogel.

36. The vaccine of claim 35, wherein said hydrogel is selected from the group consisting of an alginate, gelatin, chitosan and hyaluronic acid.

37. The vaccine of claim 35, wherein said hydrogel is selected from the group consisting of polyvinylpyrrolidone and carboxymethyl cellulose.

38. The vaccine of claim 33, wherein said gel comprises a combination of one or more of collagen, alginate, gelatin, chitosan, hyaluronic acid, polyvinylpyrrolidone and carboxymethyl cellulose.

39. The vaccine of claim 33, wherein said gel is crosslinked.

40. The vaccine of claim 24, further comprising an additive.

41. The vaccine of claim 40, wherein said additive is polyethylene glycol.

42. The vaccine of claim 24, wherein said encapsulation vehicle comprises a microcapsule.

43. The vaccine of claim 24, wherein said encapsulation vehicle comprises a nanocapsule.

44. The vaccine of claim 24, wherein said encapsulation vehicle comprises a nanotube.

45. The vaccine of claim 44, wherein said nanotube has a diameter of 500 nm or less.

46. The vaccine of claim 24, wherein said encapsulation vehicle comprises a combination of one or more of a solution, a powder or a gel.

47. The vaccine of claim 24, wherein said virus is a live virus.

48. The vaccine of claim 24, wherein said virus is an attenuated virus.

49. The vaccine of claim 24, wherein said virus is a killed virus.

50. The vaccine of claim 24, wherein said virus is a respiratory virus.

51. The vaccine of claim 24, wherein said virus is selected from the group consisting of an orthomyxovirus, a paramyxovirus, a coronavirus, a picomavirus, respiratory syncytial virus, measles virus, adenovirus, a parvovirus, and adenovirus, a calicivirus, an astrovirus, Norwalk virus, an arenavirus, a flavivirus, a filovirus, a hantavirus, an alphavirus, a retrovirus and a lentivirus.

52. The vaccine of claim 51, wherein said virus is an orthomyxovirus.

53. The vaccine of claim 52, wherein said orthomyxovirus is an influenza virus.

54. The vaccine of claim 53, wherein said influenza virus is influenza virus type A.

55. The vaccine of claim 54, wherein said influenza virus type A has a hemagglutinin antigen (HA) selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 and H16.

56. The vaccine of claim 54, wherein said influenza virus type A has a neuraminidase antigen (NA) selected from the group consisting of N1, N2, N3, N4, N5, N6, N7, N8 and N9.

57. The vaccine of claim 54, wherein said influenza virus type A has a HA:

NA antigenic profile selected from the group consisting of H5N1, H9N2, H7N1, H7N2, H7N3, H7N7, H2N2, H1N1, H1N2 and H3N2.

58. The vaccine of claim 54 comprising a low dose of said influenza virus type A.

59. The vaccine of claim 58, wherein said low dose of influenza type A virus is from 0.001 to 5000 hamagglutination units (HAU) of virus.

60. The vaccine of claim 59, wherein said low dose of influenza virus type Amis from 0.005 to 500 HAU of virus.

61. The vaccine of claim 60, wherein said low dose of influenza virus type A is from 0.01 to 100 HAU of virus.

62. The vaccine of claim 24, wherein said animal is a mammal.

63. The vaccine of claim 62, wherein said mammal is a human.

64. The vaccine of claim 24, wherein said virus comprises a combination of two or more of a live virus, an attenuated virus, and a killed virus.

65. The vaccine of claim 24, wherein said route is a non-natural route.

66. The vaccine of claim 65, wherein said route at least one member selected from the group consisting of subcutaneous, intradermal, intramuscular, mucosal and oral.

67. A kit comprising the vaccine of claim 24.

25. A vaccine comprising a CD8+ T cell immunoprotective amount of virus, wherein said virus induces an immunoprotective CD8+ T cell response in an animal following administration of said virus to said animal by a route that does not cause disease in said animal, and further wherein said virus is associated with an encapsulation vehicle.

68. A device for delivery of a vaccine to an animal, said device comprising (a) a CD8+ T cell immunoprotective and/or antibody amount of virus, wherein said virus induces an immunoprotective CD8+ T cell and/or antibody response in an animal following administration of said virus to said animal by a non-natural route, (b) a delivery device for delivering said vaccine to said animal.

70. The device of claim 68, wherein said delivery device comprises a hollow tube.

71. The device of claim 70, wherein said hollow tube has a tapered end.

72. The device of claim 71, wherein said delivery device comprises a needle.

73. The device of claim 70, wherein said hollow tube is optionally attached to a plunging device.

74. The device of claim 73, wherein said plunging device is a syringe.

75. The device of claim 68, wherein said delivery device is a gene gun.

76. The device of claim 68, wherein said delivery device is a catheter.

77. The device of claim 68, wherein said delivery device is a patch.

78. The device of claim 68, wherein said delivery device is an inhaler.

79. The device of claim 68, wherein said delivery device is a mucosal applicator.

80. The device of claim 68, further comprising an encapsulation vehicle.

81. The device of claim 80, wherein said virus is encapsulated in said encapsulation vehicle.

82. The device of claim 80 wherein said virus is associated with a nanotube, a lipsome or a protein prior to being encapsulated in said encapsulation vehicle.

83. The device of claim 80, wherein said encapsulation vehicle is one or more members selected from the group consisting of a gel, a liquid or a powder.

84. The device of claim 83, wherein said encapsulation vehicle is loaded into a nanotube.

85. The device of claim 80, wherein said encapsulation vehicle comprises a polymer.

86. The device of claim 85, wherein said polymer is not toxic when administered to an animal.

87. The device of claim 86, wherein said polymer is associated with said virus thereby delaying release of said virus into the surrounding environment.

88. The device of claim 85, wherein said polymer is a gel.

89. The device of claim 88, wherein said gel comprises collagen.

90. The device of claim 88, wherein said gel is a hydrogel.

91. The device of claim 90, wherein said hydrogel is selected from the group consisting of an alginate, gelatin, chitosan and hyaluronic acid.

92. The device of claim 90, wherein said hydrogel is selected from the group consisting of polyvinylpyrrolidone and carboxymethyl cellulose.

93. The device of claim 88, wherein said gel comprises a combination of one or more of collagen, alginate, gelatin, chitosan, hyaluronic acid, polyvinylpyrrolidone and carboxymethyl cellulose.

94. The device of claim 88, wherein said gel is crosslinked.

95. The device of claim 80, further comprising an additive.

96. The device of claim 95, wherein said additive is polyethylene glycol.

97. The device of claim 80, wherein said encapsulation vehicle comprises a microcapsule.

98. The device of claim 80, wherein said encapsulation vehicle comprises a nanocapsule.

99. The device of claim 80, wherein said encapsulation vehicle comprises a nanotube.

100. The device of claim 99, wherein said nanotube has a diameter of 500 nm or less.

101. The device of claim 80, wherein said encapsulation vehicle comprises a combination of one or more of a solution, a powder or a gel.

102. The device of claim 80, wherein said virus is a live virus.

103. The device of claim 80, wherein said virus is an attenuated virus.

104. The device of claim 80, wherein said virus is a killed virus.

105. The device of claim 80, wherein said virus is a respiratory virus.

106. The device of claim 80, wherein said virus is selected from the group consisting of an orthomyxovirus, a paramyxovirus, a coronavirus, a picornavirus, respiratory syncytial virus, measles virus, adenovirus, a parvovirus, and adenovirus, a calicivirus, an astrovirus, Norwalk virus, an arenavirus, a flavivirus, a filovirus, a hantavirus, an alphavirus, a retrovirus and a lentivirus.

107. The device of claim 106, wherein said virus is an orthomyxovirus.

108. The device of claim 107, wherein said orthomyxovirus is an influenza virus.

109. The device of claim 108, wherein said influenza virus is influenza virus type A.

110. The device of claim 109, wherein said influenza virus type A has a hemagglutinin antigen (HA) selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 and H16.

111. The device of claim 109, wherein said influenza virus type A has a neuraminidase antigen (NA) selected from the group consisting of N1, N2, N3, N4, N5, N6, N7, N8 and N9.

112. The device of claim 109, wherein said influenza virus type A has a HA:

NA antigenic profile selected from the group consisting of H5N1, H9N2, H7N1, H7N2, H7N3, H7N7, H2N2, H1N1, H1N2 and H3N2.

113. The device of claim 109 comprising a low dose of said influenza virus type A.

114. The device of claim 113, wherein said low dose of influenza type A virus is from 0.001 to 5000 hamagglutination units (HAU) of virus.

115. The device of claim 114, wherein said low dose of influenza virus type Amis from 0.005 to 500 HAU of virus.

116. The device of claim 115, wherein said low dose of influenza virus type A is from 0.01 to 100 HAU of virus.

117. The device of claim 80, wherein said animal is a mammal.

118. The device of claim 117, wherein said mammal is a human.

119. The device of claim 80, wherein said virus comprises at least two members selected from the group consisting of a live virus, an attenuated virus, and a killed virus.

120. The device of claim 80, wherein said route is a non-natural route.

121. The device of claim 120, wherein said route is at least one members selected from the group consisting of subcutaneous, intradermal, intramuscular, mucosal and oral.

69. A device for delivery of a vaccine to an animal, said device comprising (a) a CD8+ T cell immunoprotective amount of virus, wherein said virus induces an immunoprotective CD8+ T cell response in an animal following administration of said virus to said animal by a non-natural route, (b) a delivery device for delivering said vaccine to said animal.

122. A method of making a vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of virus, said method comprising combining a CD8+ T cell and/or antibody immunoprotective amount of a virus with an encapsulation vehicle, thereby making said vaccine.

123. A method of making a vaccine comprising a CD8+ T cell immunoprotective amount of virus, said method comprising combining an immunoprotective amount of a virus with an encapsulation vehicle, thereby making said vaccine.

124. A method of eliciting a CD8+ T cell immunoprotective and/or antibody immune response in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell and/or antibody immunoprotective amount of virus, whereby a CD8+ T cell and/or antibody immune response is elicited in said mammal.

126. The method of claim 124, wherein said animal is a mammal.

127. The method of claim 126, wherein said mammal is a human.

125. A method of eliciting a CD8+ T cell immune response in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective amount of virus, whereby a CD8+ T cell immune response is elicited in said animal.

128. A method of protecting an animal against infection by a virus, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of said virus, whereby a CD8+ T cell and/or antibody immune response is elicited in said animal thereby protecting said animal against said infection.

130. The nethod of claim 128, wherein said animal is a mammal.

131. The method of claim 130, wherein said mammal is a human.

129. A method of protecting an animal against infection by a virus, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective amount of said virus, whereby a CD8+ T cell immune response is elicited in said animal thereby protecting said animal against said infection.

132. A method of preventing a virus infection in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of said virus, whereby a CD8+ T cell and/or antibody immune response is elicited in said animal thereby preventing a virus infection in said animal.

134. The method of claim 132, wherein said animal is a mammal.

135. The method of claim 134, wherein said mammal is a human.

133. A method of preventing a virus infection in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective amount of said virus, whereby a CD8+ T cell immune response is elicited in said animal thereby preventing a virus infection in said animal.

136. A method of treating a virus infection in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of said virus, whereby a CD8+ T cell and/or antibody immune response is elicited in said animal thereby treating said animal.

138. The method of claim 136, wherein said animal is a mammal.

139. The method of claim 138, wherein said mammal is a human.

137. A method of treating a virus infection in an animal, said method comprising administering to said animal a vaccine comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of said virus, whereby a CD8+ T cell and/or antibody immune response is elicited in said animal thereby treating said animal.

140. A composition comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of a bioactive agent, wherein said bioactive agent induces an immunoprotective CD8+ T cell and/or antibody response in an animal following administration of said bioactive agent to said animal by a route that does not cause disease in said animal.

142. The composition of claim 140, wherein said route is a non-natural route.

143. The composition of claim 140, wherein said route is selected from the group consisting of subcutaneous, intradermal, intramuscular, mucosal and oral.

144. The composition of claim 140, wherein said bioactive agent is encapsulated in said encapsulation vehicle.

145. The composition of claim 140, wherein said bioactive agent is associated with a nanotube, a lipsome or a protein prior to being encapsulated in said encapsulation vehicle.

146. The composition of claim 140, wherein said encapsulation vehicle comprises at least one member selected from the group consisting of a gel, a liquid or a powder.

147. The composition of claim 146, wherein said encapsulation vehicle is loaded into a nanotube.

148. The composition of claim 147, wherein said encapsulation vehicle comprises a polymer.

149. The composition of claim 148, wherein said polymer is not toxic when administered to an animal.

150. The composition of claim 148, wherein said polymer is associated with said bioactive agent thereby delaying release of said bioactive agent into the surrounding environment.

151. The composition of claim 148, wherein said polymer is a gel.

152. The composition of claim 140, wherein said bioactive agent is selected from the group consisting of a microorganism, and a protein.

141. A composition comprising a CD8+ T cell immunoprotective amount of bioactive agent, wherein said bioactive agent induces an immunoprotective CD8+ T cell response in an animal following administration of said bioactive agent to said animal by a route that does not cause disease in said animal.

153. A method of enhancing safety when administering a bioactive agent to an animal, said method comprising administering a composition comprising a CD8+ T cell immunoprotective and/or antibody immunoprotective amount of a bioactive agent to said animal, wherein said bioactive agent induces an immunoprotective CD8+ T cell and/or antibody response in said animal following administration of said bioactive agent by a route that does not cause disease in said animal and further wherein said bioactive agent is encapsulated in an encapsulation vehicle.

155. The method of claim 153, wherein said bioactive agent is selected from the group consisting of a microorganism and a protein.

154. A method of enhancing safety when administering a bioactive agent to an animal, said method comprising administering to said animal a composition comprising a CD8+ T cell immunoprotective amount of bioactive agent, wherein said bioactive agent induces an immunoprotective CD8+ T cell response in said animal following administration of said bioactive agent by a route that does not cause disease in said animal and further wherein said bioactive agent is encapsulated in an encapsulation vehicle.

156. A composition comprising a biologically effective amount of a bioactive agent, wherein said bioactive agent induces a desired response in an animal while reducing risk in an animal following administration of said bioactive agent to said animal by a route that does not cause disease in said animal.

157. The composition of claim 156, wherein said route is a non-natural route.

158. The composition of claim 157, wherein said route is selected from the group consisting of subcutaneous, intradermal, intramuscular, mucosal and oral.

159. The composition of claim 156, wherein said bioactive agent is encapsulated in an encapsulation vehicle.

160. The composition of claim 156, wherein said bioactive agent is associated with a nanotube, a liposome or a protein prior to being encapsulated in said encapsulation vehicle.

161. The composition of claim 156, wherein said encapsulation vehicle is at least one member selected from the group consisting of a gel, a liquid or a powder.

162. The composition of claim 159, wherein said encapsulation vehicle is loaded into a microcapsule, nanocapsule or nanotube.

163. The composition of claim 159, wherein said encapsulation vehicle comprises a polymer.

164. The composition of claim 163, wherein said polymer is not toxic when administered to an animal.

165. The composition of claim 163, wherein said polymer is associated with said bioactive agent thereby delaying release of said bioactive agent into the surrounding environment.

166. The composition of claim 163, wherein said polymer is a gel.

167. The composition of claim 156, wherein said bioactive agent is selected from the group consisting of a microorganism, and a protein.

168. A method of enhancing safety when administering a bioactive agent to an animal, said method comprising administering to an animal a composition comprising an amount of a bioactive agent that induces a desired response while reducing risk in an animal, wherein the route of administration of said bioactive agent is a route that does not cause disease in said animal, and further wherein said bioactive agent is encapsulated in an encapsulation vehicle thereby enhancing safety when administering said bioactive agent.