Vaccine nanotechnology
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.
1. A method of making nanoparticles comprising mixing in a defined ratio a first amphiphilic polymer having a hydrophobic end and a hydrophilic end with a second polymer, wherein at least some of the first amphiphilic polymer or the second polymer, or both the first amphiphilic polymer and second polymer, have antigen and/or an immunomodulatory agent bound thereto,
under conditions wherein nanoparticles form with the hydrophobic end of the first amphiphilic polymer oriented within the nanoparticle to form a hydrophobic interior, and the hydrophilic end of the first amphiphilic polymer is oriented to the outside of the nanoparticle, so that the antigen and/or an immunomodulatory agent is present on the surface,
wherein the nanoparticles have a diameter between 50 nm and 500 nm.
2. The method of claim 1 wherein the immunomodulatory agent is selected from the group consisting of CpG sequences, cholera toxin, monophosphoryl lipid A, imidazoquinoline, CD40 agonists, cytokines, complement receptor agonists, TGF-β, rapamycin, retinoic acid, cyclosporin, a steroid, and methotrexate.
3. The method of claim 1 wherein the nanoparticles comprise a targeting moiety on the surface targeting the nanoparticles to secondary lymphoid tissue or cells therein.
4. The method of claim 3 wherein the targeting moiety is a molecule that binds to CD11b, CD169, mannose receptor, DEC-205, CD11c, or CD21/35.
5. The method of claim 3 wherein the targeting moiety is specifically binds to targets on cells in the lymphoid tissue.
6. The method of claim 3 or 5 wherein the targeting moiety targets dendritic cells, macrophages, T cells or B cells.
7. The method of claim 1 wherein the antigen is a T cell antigen and the immunomodulatory agent is a toll-like receptor agonist.
8. The method of claim 1 wherein the antigen is a B and/or T cell antigen selected from the group consisting of proteins, lipids, carbohydrates, nucleic acid, metals and inorganic molecules.
9. The method of claim 8 wherein the B or T cell antigen is selected from the group consisting of infectious disease antigens, degenerative disease antigens, cancer antigens, atopic disease antigens, autoimmune disease antigens, allergens, and allo or xeno antigens.
10. The method of claim 9 wherein the B-cell antigen is a small molecule addictive substance or toxin.
11. The method of claim 10 wherein the B-cell antigen is nicotine and the immunomodulatory agent is a toll-like receptor agonist.
12. The method of claim 1 wherein the antigen is a B cell antigen of bacterial, viral, protozoan, parasite or fungal origin.
13. The method of claim 12 wherein the bacterial antigen is selected from the group consisting of diphtherial antigens and tetanus antigens and the viral antigen is selected from the group consisting of adenoviral and vesicular stomatitis viral peptides.
14. The method of claim 1 wherein the nanoparticles comprise a T cell antigen, wherein the T cell antigen is a self antigen, cancer antigen or allergenic peptide.
15. The method of claim 1 wherein the nanoparticles have incorporated therein T cell antigen in combination with an immunomodulatory agent, and have B cell antigen on the surface.
16. The method of claim 1 wherein the second polymer is a hydrophobic polymer.
17. The method of claim 1 wherein the first amphiphilic polymer, or second polymer, or both the first amphiphilic polymer and second polymer, are biodegradable.
18. The method of claim 17 wherein the biodegradable polymer is selected from the group consisting of polymers of lactic acid, glycolic acid, polyethylene glycol, polyethylene oxide, copolymers and block copolymers thereof.