Vaccines against intracellular pathogens using antigens encapsulated within biodegradable-biocompatible microspheres

• US RE40,786 E1
• Filed: 06/02/2000
• Issued: 06/23/2009
• 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: Birx, Deborah L., Setterstrom, Jean A., Burnett, Paul R., Van Cott, Thomas C., van Hamont, John E., Reid, Robert H.
• Primary Examiner(s): Wang; Shengjun
• Application Number:
  US09/586,747
• Time in Patent Office: 3,308 Days
• Field of Search: 424/499, 424/422, 424/426, 424/455, 424/486, 424/488, 424/418
• US Class Current: 424/499
• 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 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: C07K 14/245 Escherichia (G)

Abstract

This invention relates to parenteral and mucosal vaccines against diseases caused by intercellular pathogens using antigens encapsulated within a biodegradable-biocompatible microspheres(matrix).

Claims

1. An immunostimulating composition comprising encapsulating encapsulated microspheres comprised of (a) a biodegradable-biocompatible poly(DL-lactide-co-glycolideas poly(DL-lactide-co-glycolide) as the bulk matrix produced by a solvent evaporation process wherein the molecular weight of the copolymer is between 4,000 to 100,000 daltons and (b) an immunogenic substance consisting of a conformationally native subunit of chronic intracellular pathogen which, in the course of natural infection with that pathogen, is exposed to the host immune system on the surface of free pathogen and/or pathogen-infected cells.

2. The immunostimulating composition described in claim 1 wherein the immunogenic substance is an antigen and the antigen is pre-encapsulated into a conformationally stabilizing hydrophilic matrix consisting of an appropriate mono, di- or tri-saccharide or other carbohydrate susbstance substance by lyophilization prior to its final encapsulation into the PLG microsphere by a solvent extraction process employing acetonitrile as the polymer solvent, mineral oil as the emulsion'"'"'s external phase, and heptane as the extractant.

3. The immunostimulating compositions composition described in claims claim 1 or 2 wherein the immunogenic substance is a native (oligomeric)HIV-1 envelope antigen that is conformationally stabilized by the polymer matrix and serves to elicit in animals the production of HIV specific cytotoxic T lumphocytes lymphocytes and antibodies preferentially reactive against native HIV-1 envelope antigen.

4. The immunostimulating compositions composition described in claim 3 wherein the amount of said immunogenic substance within the microcapsule comprises between 0.5% to 5.0% of the weight of said composition.

5. The immunostimulating compositions describe composition described in claim 4 wherein the relative ratio between the amount of the lactide:

glycolide components of said matrix is within the range of 52;

48 to 0;

100.

6. The immunostimulating compositions composition described in claim 5 wherein the molecular weight of said copolymer is between 4,000 to 50,000 daltons.

7. A vaccine consisting of a blend of the immunostimulating compositions described in claims 5 or 6 composition of claim 5.

8. The immunostimulating compositions composition described in claim 5, employed as a parentally parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between 1 nanometer and 20 microns.

9. The immunostimulating compositions composition described in claim 5, employed as a mucosal vaccine wherein the size of more than 50% (by volume) of said vaccine microspheres is between 5 microns to 10 microns in diameter.

10. A composition in accordance with claim 1 wherein the microspheres further contain a pharmaceutically-acceptable adjuvant.

11. A vaccine consisting of a blend of the immunostimulating compositions described in claims 5 or composition of claim 6.

12. The immunostimulating compositions composition described in claim 6 employed as a parentally parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between 1 nanometer and 20 microns.

13. The immunostimulating compositions composition described in claim 7 employed as a parentally parenterally administered vaccine wherein the diameter size range of said vaccine microspheres lies between nanogram nanometer and 20 microns.

14. The immunostimulating compositions composition described in claim 6 employed as a mucosal vaccine wherein the size of more than 50% (by volume) of said vaccine microspheres is between 5 microns to 10 microns in diameter.