Composition comprising immunogenic microparticles
The invention provides an immunogenic composition comprising at least one antigen in association with micropar-tides, wherein the microparticles are in the same size range as viruses. In addition the invention also provides vaccine compositions and methods of eliciting immune responses in a subject.
1. An immunogenic composition comprising microparticles having a solid core and an average diameter of from about 0.03 μm to about 0.05 μm and antigen covalently bound to their outer surface, the immunogenic composition, upon immunization of a human or animal subject, producing a cellular immune response to the antigen.
2. The composition of claim 1 wherein the microparticles are of substantially uniform size.
3. The composition of claim 1 wherein the microparticles are selected from the group consisting of latex, ferrous molecules, gold, glass, calcium phosphate, polystyrene, polylysine G, biodegradable polymers, biocompatible polymers, and combinations thereof.
4. The composition of claim 1 wherein the microparticles are capable of being taken up by antigen presenting cells in an animal.
5. A vaccine comprising the composition of claim 1 .
6. The composition of claim 1 wherein the antigen is selected from the group consisting of peptide, protein, lipid, carbohydrate, nucleic acid, and combinations thereof.
7. The composition of claim 1 wherein the antigen is derived from a pathogen, tissue, cell organ or molecule and is selected from the group consisting of: pollen, hepatitis C virus (HCV) core, E1, E2 and NS2 proteins, antigens from Plasmodium species selected from the group consisting of P. vivax, P. faliciparum circumsporozoite protein (CS), human P. falciparum, P. vivax, P. ovalae , and P. malariae , TRAP, MSP-1, MSP-2, MSP-3, MSP-4, MSP-5, AMA-1 RESA, SALSA, STARP, LSAT and LSA3, HIV-gp120/160 envelope glycoprotein, streptococcus surface protein antigen, influenza nucleoprotein, hemagglutinin-neuraminidase surface infection, TcpA pilin subunit, VP1 protein, LMCV nucleoprotein, Leishmania major surface glycoprotein (gp63), Bordetella pertussis surface protein, rabies virus G protein, Streptococcus M protein, Staphylococcal proteins, Helicobacter pylori proteins, Syncyticial virus (RSV) F or G proteins, Epstein Ban virus (EBV) gp340 or nucleoantigen 3A, hemagglutinin, Borrelia burgdoferi outer surface protein (Osp) A, Mycobacterium tuberculosis 38 kD lipoprotein or 30 kD protein (Ag85), 10 kD or 65 kD proteins, Neisseria meningitidis class 1 outer protein, Varicella zoster virus IE62 and gpl, Rubella virus capsid protein, Hepatitis B virus pre S1 ag, Herpes simplex virus type 1 glycoprotein G or gp D or CP27, Murray valley encephalitis virus E glycoprotein, Hepatitis A virus VP1, polio virus capsid protein VP1, VP2 and VP3, Chlamydia trachomatis surface protein, Hepatitis B virus envelope Ag pre S2, Human rhinovirus (HRV) capsid, papillomavirus peptides from oncogene E6 and E7, Listeria surface protein, Varicella virus envelope protein, Vaccinia virus envelope protein, Brucella surface protein, Rotavirus, VP-3, VP-4, VP-5, VP-7 and VP-8, combination of one or more of the antigens, an amino acid subunit of the antigen comprising five or more amino acids in length, and combinations of one or more of the subunits.
8. The composition of claim 1 wherein the antigen is breast cancer antigen, lung cancer antigen, pancreatic cancer antigen, colon cancer antigen, and melanoma cancer antigen.
9. The composition of claim 8 wherein the antigen is a recombinant peptide or protein.
10. The composition of claim 1 , wherein upon immunization of a human or animal subject, the composition further provides a humoral response, wherein the humoral response is selected from immunoglobulin G, immunoglobulin M or immunoglobulin A to the antigen.
11. The composition of claim 1 , wherein the cellular immune response includes a CD8 cellular response.
12. The composition of claim 11 , wherein the cellular immune response is elicited following a single administration of the composition.
13. The composition of claim 1 , wherein the cellular immune response is promoted by proliferation and/or expansion and/or maturation and/or stimulation of dendritic cells following uptake of the microparticles by the dendritic cells.
14. The composition of claim 13 , wherein the dendritic cells are DEC205+, CD40+ and CD86+.
15. The composition of claim 1 , wherein the microparticles have an average diameter of from about 0.04 μm to about 0.05 μm.
16. The composition of claim 15 , wherein the microparticles are polystyrene.
17. The composition of claim 1 , wherein following covalent attachment of the antigen, the microparticles are quenched with a quenching agent selected from glycine, an alcohol, an amine, or an aldehyde.
18. The composition of claim 17 , wherein the quenching agent is glycine.
19. An immunogenic composition comprising polystyrene or glass microparticles having a solid core, an average diameter of from about 0.04 μm to about 0.05 μm and antigen covalently bound to their outer surface, the immunogenic composition, upon immunization of a human or animal subject, promoting uptake of the microparticles by dendritic cells.