Vaccine nanotechnology

• US 9,539,210 B2
• Filed: 03/15/2013
• Issued: 01/10/2017
• Est. Priority Date: 10/12/2007
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Original Assignee: Brigham and Women's Hospital Incorporated, Children's Medical Center Corporation, President and Fellows of Harvard College (Harvard Corporation), Massachusetts Institute of Technology
• Inventors: von Andrian, Ulrich H., Farokhzad, Omid C., Langer, Robert S., Junt, Tobias, Moseman, Elliott Ashley, Zhang, Liangfang, Basto, Pamela, Iannacone, Matteo, Alexis, Frank
• Primary Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US13/844,382
• Publication Number:
  US 20140314865A1
• Time in Patent Office: 1,397 Days
• Field of Search: 424/501, 424/184.1, 424/275.1, 424/489
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/555 characterised by a specific combination antigen/adjuvant
• CPC Class Codes: A61K 2039/55555 Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
• CPC Class Codes: A61K 2039/60 characteristics by the carrier linked to the antigen
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4612 B-cells
• CPC Class Codes: A61K 39/4622 Antigen presenting cells
• CPC Class Codes: A61K 39/4632 T-cell receptors [TCR]; antibody T-cell receptor constructs
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/30 : for treating abuse or dependence
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/06 : for tuberculosis
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides vaccine nanocarriers capable of stimulating an immune response in T cells and/or B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at last one targeting moiety and optionally at least one immunostimulatory agent. The invention provides pharmaceutical compositions comprising inventive vaccine nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive vaccine nanocarriers and pharmaceutical compositions thereof. The invention provides methods of prophylaxis and/or treatment of diseases, disorders, and conditions comprising administering at least one inventive vaccine nanocarrier to a subject in need thereof.

Claims

1. A composition to induce tolerance to an antigen comprising polymeric nanocarriers having a diameter of between 60 nm and 400 nm, formed from the self-assembly of polymers selected from the group consisting of polyhydroxyacids, polyanydrides, polyethylene glycols, polyoxyethyleneoxides, poly(ortho esters), poly(caprolactones), polylysines, poly(ethylene imines), copolymers and block copolymers thereof,

Wherein the nanoparticles selectively target the subcapsular macrophages and dendritic cells in the draining lymph nodes, and

wherein the nanocarriers comprise

(i) immunosuppressant selected from the group consisting of TGF-β

, a rapamycin, retinoic acid, cyclosporin, steroids, and methotrexate encapsulated in the nanocarriers,

(ii) an antigen selected from the group consisting of allergic antigens and autoantigens, the antigen encapsulated within the nanocarrier, on the surface of the nanocarriers, or bound to a polymer from which the nanocarriers are formed; and

Wherein the nanocarriers are in an effective amount to induce tolerance to the antigen when administered to a human or animal.

2. The composition of claim 1 wherein the antigen is a T cell antigen.

3. The composition of claim 1 wherein the antigen is a B cell antigen.

4. The composition of claim 1 wherein the composition induces regulatory T cells which block or suppress an immune response.

5. The composition of claim 1 wherein the immunosuppressant agent is a rapamycin.

6. The composition of claim 1 comprising an allergic antigen selected from the group consisting of pollens, venoms, animal dander, fungal spores, drug and food allergens.

7. The composition of claim 1 comprising an autoantigen selected from the group consisting of antigens implicated in lupus, multiple sclerosis, rheumatoid arthritis, diabetes mellitus type I, inflammatory bowel disease, thyroiditis, and celiac disease.

8. The composition of claim 1, wherein the nanocarriers comprise polymer selected from the group consisting of copolymers and block copolymers of polyethylene glycol or polyoxyethyleneoxide with polymers of lactic acid, polymers of glycolic acid, polylactide-co-glycolide PLGA, poly(ortho ester), poly(caprolactone), polylysine, poly(ethylene imine), and copolymers and block copolymers thereof.

9. A method of therapeutically or prophylactically treating an individual in need thereof comprising administering to the individual or dendritic cells isolated therefrom an effective amount of the nanocarriers of claim 1 to promote tolerance to the antigen in a subject.

10. The method of claim 9 wherein the individual is susceptible to having an allergic disease or an autoimmune disease.

11. The method of claim 10 wherein the individual has a food allergy.

12. The method of claim 11 wherein the food allergy is against milk or other milk components , eggs, peanuts, tree nuts , fish, shellfish, soy, or wheat.

13. The method of claim 10 wherein the autoimmune disease is selected from the group consisting of lupus, multiple sclerosis, rheumatoid arthritis, diabetes mellitus type I, inflammatory bowel disease, thyroiditis, and celiac disease.

14. The method of inducing tolerance of claim 10 comprising exposing dendritic cells in culture to the nanoparticles to induce antigen-specific tolerogenic dendritic cells and administering the cells to an individual in need thereof.

15. The composition of claim 1, wherein the nanocarriers comprise an amphiphilic polymer.

16. The composition of claim 1, wherein the immunosuppressant is both on the surface of the nanocarrier and encapsulated within the nanocarrier.

17. The composition of claim 16 wherein the immunsosuppresssant on the surface of the nanocarrier is different from the immunosuppressant Encapsulated within the nanocarrier.