Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres

• US 5,417,986 A
• Filed: 04/10/1992
• Issued: 05/23/1995
• Est. Priority Date: 03/16/1984
• Status: Expired due to Fees

• Current Assignee: United States Army (U.S. Department Of Defense)
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Setterstrom, Jean A., van Hamont, John E., Reid, Robert H., Boedeker, Edgar C.
• Primary Examiner(s): Henley, III, Raymond J.
• Assistant Examiner(s): CRIARES, THEODORE J
• Application Number:
  US07/867,301
• Time in Patent Office: 1,138 Days
• Field of Search: 424/499, 424/422, 424/85, 424/417, 424/450, 424/458, 424/469, 424/88, 424/89, 424/92, 424/863, 424/965
• US Class Current: 424/499
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55505 Inorganic adjuvants
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/0258 Escherichia
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: C12N 2730/10134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• 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

This invention is directed to oral parenteral and intestinal vaccines and eir use against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres.

Claims

1. An immunostimulating composition comprising encapsulation-microspheres, which may contain a pharmaceutically-acceptable adjuvant, wherein said microspheres having a diameter between 1 nanometers (nm) to 10 microns (um) are comprised of (a) a biodegradable-biocompatible poly (DL-lactide-co-glycolide) or polyglycolide as the bulk matrix, wherein the relative ratio between the amount of lactide;

glycolide components are within the range of 52;

48 to 0;

100 and (b) an immunogenic substance comprising Colonization Factor Antigen and hepatitis B surface antigen that serves to elicit the production of antibodies and T-lymphocyte proliferation in animals.

2. An immunostimulating composition according to claim 1 wherein the amount of said immunogenic substance is within the range of 0.1 to 1.5% based on the volume of said bulk matrix.

3. An immunostimulating composition according to claim 2 wherein the relative ratio between the lactide and glycolide component is within the range of 48:

52 to 58;

42.

4. An immunostimulating composition according to claim 2 wherein the size of more than 50% of said microspheres is between 5 to 10 um in diameter by volume.

5. A vaccine comprising an immunostimulating composition of claim 4 and a sterile, pharmaceutically-acceptable carrier therefor.

6. A vaccine comprising an immunostimulating composition of claim 5 wherein said immunogenic substance is Colony Factor Antigen (CFA/II).

7. A vaccine comprising an immunostimulating composition of claim 5 wherein said immunogenic substance is hepatitis B surface antigen (HBsAg).

8. A method for the vaccination against bacterial infection comprising administering to a human, an antibactericidally effective amount of a composition of claim 6.

9. A method according to claim 8 wherein the bacterial infection is caused by a bacteria selected from the group consisting of Salmonella typhi, Shigela sonnei, Shigella flexneri, Shigella dysenteriae, Shigella boydii, Escheria coli, Vibrio cholera, yersinia, staphylococus, clostridium, and campylobacter.

10. A method for the vaccination against viral infection comprising administering to a human an antivirally effective amount of a composition of claim 7.

12. A method for the treatment of an animal in need thereof against infection by enteropathopathogenic organisms or hepatitis B virus comprising administering to said animal an immunogenic amount of an immunostimulating composition of claim 3.

13. A method according to claim 12 wherein the immunostimulating composition is administered orally.

14. A method according to claim 12 wherein the immunostimulating composition is administered parenterally.

11. An immunostimulating composition comprising encapsulating-microspheres, which may contain a pharmaceutically-acceptable adjuvant, wherein said microspheres having a diameter between 1 nanometers (nm) to 10 microns (um) are comprised of (a) a glycolide polymer as a bulk matrix and (b) an immunogenic substance comprising Colonization Factor Antigen and hepatitis B surface antigen that serves to elicit the production of antibodies and T-lymphocyte proliferation in animals.