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 formed of linear, branched, or dendrimeric polymer selected from the group consisting of polyanhydrides, polyhydroxyacids, polyesters and copolymers thereof, having a mean diameter of between 60 nm and 400 nm, the nanoparticles comprising:
T cell antigen selected from the group consisting of infectious disease antigens, cancer antigens, atopic disease antigens, alloantigens, and hapten, and
an immunostimmulatory agent effective to enhance the immune response to the T cell antigen,
wherein the immunostimulatory agent is selected from the group consisting of toll-like receptor (TLR) agonists, cytokine receptor agonists, CD40 agonists, Fc receptor agonists, CpG-containing nucleic acids, complement receptor agonists,
wherein the T cell antigen is encapsulated within, and/or covalently bound to the polymer forming the nanoparticles
and
wherein the immunostimulatory agent is covalently bound to the nanoparticles or to a polymer from which the nanoparticles are formed.
2. The nanoparticles of claim 1 , wherein the nanoparticles comprise B cell antigen bound to or present on the surface of the nanoparticles in a density effective to activate B cell receptors, B cell antigen encapsulated within the nanoparticles, or any combination thereof.
3. The nanoparticles of claim 1 , wherein the T cell antigen is a cancer antigen.
4. The nanoparticles of claim 1 , wherein the infectious disease antigen is a viral antigen.
5. The nanoparticles of claim 4 , wherein the viral antigen is an antigen from a pox virus, smallpox virus, ebola virus, marburg virus, dengue fever virus, influenza virus, parainfluenza virus, respiratory syncytial virus, rubeola virus, human immunodeficiency virus, human papillomavirus, varicella-zoster virus, herpes simplex virus, cytomegalovirus, Epstein-Barr virus, JC virus, rhabdovirus, rotavirus, rhinovirus, adenovirus, papillomavirus, parvovirus, picornavirus, poliovirus, virus that causes mumps, virus that causes rabies, reovirus, rubella virus, togavirus, orthomyxovirus, retrovirus, hepadnavirus, coxsackievirus, equine encephalitis virus, Japanese encephalitis virus, yellow fever virus, Rift Valley fever virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, or hepatitis E virus.
6. The nanoparticles of claim 3 , wherein the cancer antigen is selected from the group consisting of melan-A, dipeptidyl peptidase IV, adenosine deaminase-binding protein, cyclophilin b, the colorectal cancer antigen C017-1A/GA733, the carcinoembryonic antigen (CEA) and its immunogenic epitopes CAP-1 and CAP-2, etv6, aml1, prostate specific antigen (PSA) and its immunogenic epitopes PSA-1, PSA-2, and PSA-3, prostate-specific membrane antigen (PSMA), T-cell receptor/CD3-zeta chain, the MAGE-family of tumor antigens, the GAGE-family of tumor antigens, BAGE, RAGE, LAGE-1, NAG, GnT-V, MUM-1, CDK4, tyrosinase, p53, MUC family of tumor antigens, HER2/neu, p21ras, RCAS1, α-fetoprotein, E-cadherin, α-catenin, β-catenin and γ-catenin, p120ctn, gp100Pme1117, FRAME, NY-ESO-1, brain glycogen phosphorylase, SSX-1, SSX-2, SSX-1, SSX-4, SSX-5, SCP-1, CT-7, cdc27, adenomatous polyposis coli protein (APC), fodrin, P1A, Connexin 37, Ig-idiotype, p15, gp75, GM2 and GD2 gangliosides, viral products such as human papilloma virus proteins, Smad family of tumor antigens, lmp-1, EBV-encoded nuclear antigen (EBNA)-1, and c-erbB-2.
7. The nanoparticles of claim 1 , wherein the nanoparticles further comprise a targeting moiety
associated covalently or non-covalently with the surface of the nanoparticles.
8. The nanoparticles of claim 1 , formed of one or more polymers, wherein the one or more polymers is a water soluble, non-adhesive polymer, wherein the water soluble, non-adhesive polymer is a polyalkylene oxide.
9. The nanoparticles of claim 1 , wherein the nanoparticles comprise a copolymer of a water soluble, non-adhesive polymer and a biodegradable polymer.
10. The nanoparticles of claim DU 9 , wherein the biodegradable polymer is poly(lactic acid) (PLA), poly(glycol) (PGA) or poly(lactide-co-glycolic) (PLGA).
11. The nanoparticles of claim 9 , wherein the nanoparticles are formed by self-assembly.
12. The nanoparticles of claim 8 , wherein the polyalkylene oxide is a polyalkylene glycol.