Immunization implant and method

• US 5,015,476 A
• Filed: 08/11/1989
• Issued: 05/14/1991
• Est. Priority Date: 08/11/1989
• Status: Expired due to Fees

• Current Assignee: Heska Corporation (Mars Incorporated)
• Original Assignee: Paravax Incorporated
• Inventors: King, Scott R., Cochrum, Kent C., Stevenson, Lynnor B.
• Primary Examiner(s): Page, Thurman
• Assistant Examiner(s): Spear, James M.
• Application Number:
  US07/392,795
• Time in Patent Office: 641 Days
• Field of Search: 424/422, 424/423, 424/88, 424/89, 424/92, 424/93
• US Class Current: 424/423
• 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 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Antigenic parasites are encapsulated in semipermeable polymeric envelope membranes to prepare implant capsules for immunizing an animal against parasitic infection. An animal may be immunized against parasitic infection by implanting into the animal the implant capsule at a location in the animal sufficient to stimulate a protective immune response in the animal to the parasite antigen.

Claims

1. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said parasite is a mammalian parasite within the Phyla Protozoa, Platyhelminthes or Nemathelminthes.

4. The implant capsule of claim 1, wherein said polymeric envelope membrane is a polycationic polyamino acid polymer, a polyanionic polyamino acid polymer, or a combination thereof.

6. The implant capsule of claim 4, wherein said polyanionic polyamino acid is polyaspartic acid, or polyglutamic acid.

9. The implant capsule of claim 1, wherein said intermediate bonding layer is a polycationic polyamino acid

10. The implant capsule of claim 9, wherein said polycationic polyamino acid is polylysine.

2. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said parasite is an organism selected from the group consisting of parasites from the groups Toxocara, Giardia, Leishmania, Trypanosoma, Entamoeba, Toxoplasma, Plasmodium, Schistosoma, Taenia, Dipylidium, Hymenolepis, Echinococcus, Ascaris, Ancyclostomatidae, Strongylida, Trichuris, Filaroidea and Onchocerca.

3. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said parasite is selected from the group consisting of Toxocara canis, Strongylus vulgaris, Dirofilaria immitis, Fasciola hepatica, Leishmania braziliensis, Leishmania donovani, Leishmania mexicana, Trypanosoma cruzi and Toxoplasma gondii.

5. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said polymeric envelope membrane is a polycationic polyamino acid polymer, a polyanionic polyamino acid polymer, or a combination thereof and said polycationic polyamino acid is polyarginine, polylysine, or polyornithine.

7. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said polymeric envelope membrane is a polycationic polyamino acid polymer, a polyanionic polyamino acid polymer, or a combination thereof and said intermediate bonding material comprises a polysaccharide-containing material and a biocompatible gellable metal hydroxide.

8. The implant capsule of claim 7, wherein said intermediate bonding layer comprises a mixture of aluminum hydroxide with agar, agarose, alginate, or chitosan or mixtures thereof.

11. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said intermediate bonding material contains an immunologic adjuvant.

12. The implant capsule of claim 11, wherein said adjuvant is an antigenic polymer, a lymphokine or a cytokine.

13. An implant capsule for immunizing an animal against parasite infection, comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes, wherein said polymeric envelope membrane is a biocompatible biodegradable polymer selected from the group consisting of poly(lactide-co-glycolide) polymers, poly(epsiloncaprolactone) polymers and copolymers thereof, poly(hydroxybutyric acid)-poly(hydroxyvalerate) copolymers and poly(Cbz-tyrosine-tyrosinehexyl ester) iminocarbonate.

14. An implant capsule for immunizing an animal against parasitic infection, wherein said implant capsule is prepared by the steps of:

(a) suspending a parasite capable of producing antigens in an aqueous growth medium;

(b) coating said parasite with a gellable positively charged intermediate bonding material; and

(c) encapsulating said coated parasite with a polyanionic semipermeable polymeric envelope, membrane.

15. The implant capsule of claim 14, wherein said coating step is conducted by contacting said suspended parasite with a solution of aluminum hydroxide, a polycationic polyamino acid, agar, agarose, alginate, chitosan or mixtures thereof to form a coated parasite droplet.

16. The implant capsule of claim 15, wherein said coated parasite droplet is further contacted with a solution of a polyanionic polyamino acid polymer and then with a solution of a polycationic polyamino acid polymer.

17. The implant capsule of claim 16, wherein said polyanionic polyamino acid is polyaspartic acid, or polyglutamic acid and said polycationic polyamino acid is polylysine, polyarginine or polyornithine.

18. The implant capsule of claim 15, wherein said parasite is suspended in a mixture of aluminum hydroxide with at least one of agar, agarose, alginate or chitosan, and said droplets are contacted with a solution of polylysine and calcium ions, whereby said alginate is gelled and said polylysine forms said semipermeable polymeric envelope membrane.

19. The implant capsule of claim 15, wherein said parasite is suspended in the mixture of aluminum hydroxide with at least one of agar, agarose, alginate or chitosan, and said droplets are contacted with a solution of a polyanionic amino acid to encapsulate said coated parasite.

30. The method of claim 19, wherein said polymeric envelope membrane is a biocompatible biodegradable polymer selected from the group consisting of poly(lactide-co-glycolide) polymers, poly(epsilon-caprolactone) polymers and copolymers thereof, poly(hydroxybutyric acid-)poly(hydroxyvalerate) copolymers and poly(Cbz-tyrosine-tyrosine-hexyl ester) iminocarbonate.

20. A method of immunizing an animal against parasitic infection, comprising the step of implanting into an animal, an implant capsule comprising at least one antigen-producing parasite coated with a positively charged intermediate bonding material and encapsulated within one or more semipermeable polymeric envelope membranes;

at a location in said animal sufficient to stimulate a protective immune response in said animal to said parasite antigen.

21. The method of claim 20, wherein said parasite is a mammalian parasite within the Phyla Protozoa, Platyhelminthes or Nemathelminthes.

22. The method of claim 21, wherein said parasite is an organism selected from the group consisting of parasites from the groups Toxocara, Giardia, Leishmania, Trypanosoma, Entamoeba, Plasmodium, Schistosoma, Taenia, Dipylidium, Hymenolepis, Echinococcus, Ascaris, Ancyclostomatidae, Strongylida, Trichuris, Filaroidea and Onchocerca.

23. The method of claim 20, wherein said polymeric envelope membrane is a polycationic polyamino acid polymer, a polyanionic polyamino acid polymer, or a combination thereof.

24. The method of claim 23, wherein said polycationic polyamino acid is polylysine.

25. The method of claim 23, said polyanionic polyamino acid is polyaspartic acid.

26. The method of claim 20, wherein said intermediate bonding material comprises a mixture of aluminum hydroxide with agar, agarose, alginate, chitosan or mixtures thereof.

27. The method of claim 20, wherein said intermediate bonding layer is aluminum hydroxide.

28. The method of claim 20, wherein said intermediate bonding layer is a polycationic polyamino acid.

29. The method of claim 28, wherein said polycationic polyamino acid is polylysine.

31. The method of claim 20, wherein said intermediate bonding material contains an immunologic adjuvant.

32. The method of claim 31, wherein said immunologic adjuvant is an antigenic polymer, a lymphokine or a cytokine.