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. Nanoparticles having a geometric diameter of between greater than 60 nm and less than 250 nm, and formed of one or more polymers selected from the group consisting of polyesters, polyhydroxacids, poly(orthoesters); polyanhydrides, polyalkylene oxides, and copolymers thereof,
wherein the nanoparticles selectively target the subcapsular macrophages and dendritic cells in the draining lymph nodes, and
wherein the nanoparticles comprise
a dendritic cell immunomodulatory agent selected from the group consisting of toll-like receptor agonists, CD40 agonists, and agents which promote dendritic cell maturation; and
a T cell peptide antigen for processing by dendritic cells and presentation with major histocompatibility complex (MHC) to T cells.
2. The nanoparticles of claim 1 , wherein the immunomodulatory agent is covalently associated with the nanoparticle.
3. The nanoparticles of claim 1 , wherein the immunomodulatory agent is non-covalently associated with the nanoparticle.
4. The nanoparticles of claim 1 , wherein the nanoparticles comprise a lipid membrane.
5. The nanoparticles of claim 1 , wherein the polymer is an amphiphilic polymer.
6. The nanoparticles of claim 5 , wherein the hydrophobic end of the amphiphilic polymer is located within the interior of the nanoparticles.
7. The nanoparticles of claim 1 , comprising an amphiphilic entity selected from the group consisting of phosphatidylcholine, lipid A, cholesterol, dolichol, sphingosine, sphingomyelin, ceramide, cerebroside, sulfatide, phytosphingosine, phosphatidylethanolamine, glycosylceramide, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, cardiolipin, phosphatidic acid, and lysophosphatides.
8. The nanoparticles of claim 1 , wherein the T cell antigen is a degenerative disease antigen, an infectious disease antigen, or a cancer antigen.
9. The nanoparticles of claim 1 , wherein the immunomodulatory agent is a CpG-containing immunomodulatory nucleic acid.
10. The nanoparticles of claim 1 wherein the T cell antigen is covalently bound to the nanoparticles or to a polymer from which the nanoparticles are formed.
11. The nanoparticles of claim 1 further comprising a dendritic cell targeting agent selected from the group consisting of CD11b; CD169; mannose receptor; DC-205, CD11c; BDCA-1; BDCA-2; BDCA-4; class II MHC; CD80; CD86; DC-SIGN; Siglec-H; CX3 CR1; and CD21/35.
12. The nanoparticles of claim 1 , wherein the immunomodulatory agent targets the nanoparticles to secondary lymphoid tissue or organs.
13. The nanoparticles of claim 1 wherein the immunomodulatory agent is on the surface of the nanoparticle, encapsulated within the nanoparticle, or both on the surface and encapsulated within the nanoparticle.
14. The nanoparticles of claim 1 , wherein the immunomodulatory agent is a toll-like receptor agonist.
15. The nanoparticles of claim 1 having encapsulated therein T cell antigen in combination with an immunomodulatory agent.
16. The nanoparticles of claim 1 formed of a hydrophobic polymer providing a hydrophobic environment within the nanoparticles.
17. The nanoparticles of claim 1 , wherein the copolymer is made from poly(lactide-co-glycolide) and polyethylene glycol.
18. The nanoparticles of claim 1 , wherein the nanoparticles have a positive zeta potential.
19. The nanoparticles of claim 1 , wherein the nanoparticle forms by self-assembly.
20. The nanoparticles of claim 1 , wherein the zeta potential is between −25 mV and +25 mV.
21. The nanoparticles of claim 1 , wherein the immunomodulatory agent is less than 20% by weight of the nanoparticle.