Vaccine Nanotechnology

• US 20100233251A1
• Filed: 10/12/2008
• Published: 09/16/2010
• Est. Priority Date: 10/12/2007
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Massachusetts Institute of Technology
• Original Assignee: Harvard University, Immune Disease Institute Massachusetts, Massachusetts Institute of Technology, The Brigham and Women's Hospital Incorporated Massachusetts
• Inventors: Alexis, Frank, Von Andrian, Ulrich H., Moseman, Ashley, Junt, Tobias, Zhang, Liangfang, Farokhzad, Omid C., Langer, Robert S., Iannacone, Matteo, Basto, Pamela
• Granted Patent: US 10,736,848 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• 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 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001102 Receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: A61K 39/001106 Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
• CPC Class Codes: A61K 39/001151 p53
• CPC Class Codes: A61K 39/001156 Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
• CPC Class Codes: A61K 39/001158 Proteinases
• CPC Class Codes: A61K 39/001162 Kinases, e.g. Raf or Src
• CPC Class Codes: A61K 39/001166 Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
• CPC Class Codes: A61K 39/00117 Mucins, e.g. MUC-1
• CPC Class Codes: A61K 39/001171 Gangliosides, e.g. GM2, GD2 or GD3
• CPC Class Codes: A61K 39/001181 Alpha-feto protein
• CPC Class Codes: A61K 39/001182 Carcinoembryonic antigen [CEA]
• CPC Class Codes: A61K 39/001184 Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
• CPC Class Codes: A61K 39/001186 MAGE
• CPC Class Codes: A61K 39/001188 NY-ESO
• CPC Class Codes: A61K 39/001191 Melan-A/MART
• CPC Class Codes: A61K 39/001194 : Prostate specific antigen [PSA]
• CPC Class Codes: A61K 39/001195 : Prostate specific membrane antigen [PSMA]
• 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 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 in B cells, in some embodiments, comprising at least one immunomodulatory agent, and optionally comprising at least 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

1-386. -386. (canceled)

387. Nanoparticles formed of polymer or lipid having a diameter of between 40 nm and 400 nm,

having incorporated therein T cell antigens,

the nanoparticles having bound to or present on the surface B cell antigen, preferably in a density activating B cell receptors, and/or having immunomodulatory agents incorporated therein.

388. The nanoparticles of claim 387 having bound to or present on the surface an agent or material targeting the nanoparticles to secondary lymphoid tissue or cells therein.

389. The nanoparticles of claim 387 comprising a targeting agent for a molecule selected from the group consisting of CD11b, CD169, mannose receptor, DEC-205, CD11c, and CD21/35.

390. The nanoparticles of claim 387 comprising an immunomodulatory agent selected from the group consisting of specific and non-specific immunostimulants.

391. The nanoparticles of claim 390 wherein the immunomodulatory agent non-selectively targets the nanoparticles to secondary lymphoid tissue or cells therein, wherein the agent is selected from the group consisting of an adjuvant, hydrophilic polymer like polyethylene glycol or amphiphilic polymer, emulsion and liposome associated with the nanoparticles.

392. The nanoparticles of claim 387 wherein the targeting agent is selected from molecules specifically binding to targets on cells in the lymphoid tissue.

393. The nanoparticles of claim 392 wherein the targeting agent targets dendritic cells, macrophages, T cells or B cells.

394. The nanoparticles of claim 387 wherein the T cell antigen is a toll-like receptor agonist.

395. The nanoparticles of claim 387 comprising an immunomodulatory agent selected from the group consisting of CpG peptides, cholera toxin, squalene, phosphate adjuvants, tetrachlorodecaoxide, monophosphoryl lipid A, saponines, imidazoquinoline, CD40 agonists, cytokines, and complement receptor agonists.

396. The nanoparticles of claim 387 wherein the B or T cell antigen is selected from the group consisting of proteins, carbohydrates, glycoproteins, lipoproteins, lipids, nucleic acid, metals and inorganic molecules.

397. The nanoparticles of claim 396 wherein the antigen is selected from the group consisting of infectious disease antigens, degenerative disease antigens, cancer antigens, atopic disease antigens, autoimmune disease antigens, allergens, and alto or xeno antigens.

398. The nanoparticles of claim 397 wherein the B-cell antigen is a small molecule addictive substance or toxin.

399. The nanoparticles of claim 398 wherein the B-cell antigen is nicotine, the immunomodulatory agent is a toll-like receptor agonist, and the nanoparticles are formed of polymer, wherein the nicotine is optionally conjugated to the polymer.

400. The nanoparticles of claim 387 wherein the B cell antigens are of bacterial, viral, protozoan, parasite or fungal origin.

401. The nanoparticles of claim 400 wherein the bacterial antigen is selected from the group consisting of diptherial antigens and tetanus antigens and the viral antigen is selected from the group consisting of adenoviral and vesicular stomatitis viral peptides.

402. The nanoparticles of claim 387 wherein the T cell antigen is a self antigen, cancer antigen or allergenic peptide.

403. The nanoparticles of claim 388 comprising agents targeting dendritic cells, lymph node macrophages, T cells or B cells.

404. The nanoparticles of claim 387 comprising polymer having incorporated therein T cell antigen in combination with an immunomodulatory agent, and having B cell antigen on the surface of the nanoparticles.

405. The nanoparticles of claim 387 formed of a hydrophobic polymer or having a hydrophobic core.

406. The nanoparticles of claim 387 formed of a biodegradable polymer.

407. The nanoparticles of claim 406 wherein the polymer is selected from the group consisting of polymers of lactic acid, glycolic acid, polyethylene glycol, polyoxyethyleneoxide, copolymers and block copolymers thereof.

408. The nanoparticles of claim 387 comprising polymeric nanoparticles comprising antigen and targeted to phagocytic cells, in liposomes or emulsions, in combination with adjuvant.

409. The nanoparticles of claim 387 wherein one or more of the antigens, immunomodulatory agents or targeting agents is covalently bound to the nanoparticles or polymers forming the nanoparticles.

410. The nanoparticles of claim 387 wherein the nanoparticles comprise hydrophilic polymer or lipid on the surface, preferably conjugated to hydrophobic polymer within the nanoparticles.

411. A method of making the nanoparticles of claim 387 comprising forming the nanoparticle with at least a T cell antigen incorporated therein, either in combination with an immunomodulatory agent or having B cell antigen on the surface.

412. A method of therapeutically or prophylactically treating an individual in need thereof comprising administering an effective amount of the nanoparticles of claim 387 to elicit an immune response.

413. The method of claim 412 wherein the individual is in need of vaccination.

414. The method of claim 412 wherein the individual has or is at risk of developing a degenerative disease, an infectious disease, cancer, an atopic disease, an autoimmune disease, an allergy, an addiction, or a metabolic disease.

415. A nanoparticle comprising molecules selected from the group consisting of T cell antigens, B cell antigens, and immunomodulatory agents, wherein the nanoparticle is targeted to dendritic cells, lymph node macrophages, T cells or B cells.

416. A nanoparticle comprising B cell antigens on its surface in a density activating B cell receptors and an immunomodulatory agent.

417. A nanoparticle comprising molecules selected from the group consisting of T cell antigens, B cell antigens, and immunomodulatory agents, wherein the nanoparticle forms by self-assembly.