Compositions for inducing immune responses
The invention provides, inter alia, immunogenic compositions comprising a first antigen, at least two adjuvants, wherein a first adjuvant comprises a polymer derived from poly(lactides) and/or poly(lactide-co-glycolides), and wherein a second adjuvant comprises an imidazoquinoline, wherein said first antigen is encapsulated within, adsorbed or conjugated to, co-lyophilized or mixed with said first adjuvant, and a pharmaceutically acceptable excipient, wherein said composition elicits a cellular immune response when administered to a vertebrate subject. The invention also provides methods of producing immunogenic compositions, methods for producing a cytotoxic-T lymphocyte (CTL) response in a vertebrate subject, and methods of immunization.
1. An immunogenic composition comprising (a) a first antigen, (b) at least two adjuvants, wherein a first adjuvant comprises poly(lactide) polymer and/or poly(lactide-co-glycolide) polymer in the form of a particle, wherein a second adjuvant comprises an imidazoquinoline, and a pharmaceutically acceptable excipient, wherein said composition elicits a cellular immune response when administered to a vertebrate subject.
2. The immunogenic composition of claim 1 wherein said first antigen is adsorbed to the surface of said first adjuvant.
3. The immunogenic composition of claim 1 wherein said first antigen is a nucleic acid molecule.
4. The immunogenic composition of claim 3 wherein said nucleic acid molecule is DNA or RNA.
5. The immunogenic composition of claim 3 wherein said nucleic acid molecule is linked to a regulatory sequence which controls expression of said nucleic acid molecule.
6. The immunogenic composition of claim 1 wherein said first antigen is a protein.
7. The immunogenic composition of claim 6 wherein said protein is selected from the group consisting of a viral, fungal, bacterial, avian and mammalian protein.
8. The immunogenic composition of claim 6 wherein said protein is a viral protein selected from the group comprising a herpes simplex virus type 2 protein, a hepatitis C virus (HCV) protein, a meningococcal antigen, an influenza A virus protein, a human immunodeficiency virus (HIV) protein, an immunogenic fragment of any of the foregoing or combinations thereof.
9. The immunogenic composition of claim 6 wherein said protein is a bacterial protein selected from the group consisting of a pertussis protein, a diphtheria protein, an N. meningitidis protein, an H. pylori protein, an H. influenza B protein, a tetanus protein, an immunogenic fragment of the foregoing, or combinations thereof.
10. The immunogenic composition of claim 6 wherein said protein is an HCV antigen selected from the group consisting of an HCV core protein, E1, E2, NS3, NS4, NS5, an immunogenic fragment of the foregoing or combinations thereof.
11. The immunogenic composition of claim 6 wherein said protein is an HIV antigen selected from the group consisting of gp120, gp160, gp41, p24gag or p55gag, an immunogenic fragment of the foregoing, or combinations thereof.
12. The immunogenic composition of claim 6 wherein said protein is selected from the group comprising an HCV E1E2 polypeptide, an N. meningitidis ORF 287 polypeptide, an N. meningitidis ORF 961 polypeptide, HSVgB2, gp120, p55gag, an immunogenic fragment of the foregoing or combinations thereof.
13. The immunogenic composition of claim 1 wherein at least one adjuvant is present in an amount from about 0.01% to about 2% w/v.
14. The immunogenic composition of claim 1 wherein the imidazoquinoline is R-848.
15. The immunogenic composition of claim 1 comprising a further adjuvant selected from the group consisting of aluminum salts, MF59, SAF, an adjuvant system comprising squalene and one or more bacterial cell wall components, saponin adjuvants, Complete Freunds Adjuvant (CFA), Incomplete Freunds Adjuvant (IFA), one or more cytokines, macrophage colony stimulating factor (M-CSF), tumor necrosis factor (TNF), VEGF, CD27, CD30, CD40, Fas Ligand, Placenta Growth Factor, detoxified mutants of a bacterial ADP-ribosylating toxin, CpG adjuvants, PT-K9/G129, or combinations thereof.
16. A method of eliciting an immune response in a vertebrate subject comprising administering to the vertebrate subject a effective amount of the immunogenic composition according to claim 1 .
17. The method of claim 16 wherein the vertebrate subject is a human.
18. The method of claim 16 wherein the immunogenic composition is delivered by a device selected from the group consisting of a particle accelerator, a pump, an intradermal applicator, a biolistic injector, a pneumatic injector, a sponge depot, a pill, and a tablet.
19. The method of claim 16 wherein the immunogenic composition is delivered by needle-free injection.
20. An immunogenic composition comprising a first antigen, at least two adjuvants, wherein a first adjuvant comprises a polymer derived from poly(lactides) and/or poly(lactide-co-glycolides), and wherein a second adjuvant comprises an imidazoquinoline, and a pharmaceutically acceptable excipient, wherein the first antigen is a particle produced by a process comprising the steps of: (a) adding a precipitation agent to an aqueous solution of an antigen and stirring the resulting mixture to form the particle; (b) stabilizing the antigen particle by a stabilizing treatment; and (c) recovering the antigen particle from the aqueous solution.
21. A stabilized particle capable of eliciting a cytotoxic-T lymphocyte (CTL) response, wherein the stabilized particle is a generally spherical particle that is produced by a process comprising: (a) forming a particle from antigen; (b) stabilizing the particle by a stabilizing treatment, wherein the stabilized particle is not a virus-like particle, and wherein the stabilized particle is not entrapped within a carrier; and (c) adding an adjuvant comprising an imidazoquinoline.