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 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.
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.