Antigenic compositions and methods
Multilayer films comprised of polypeptide epitopes and a toll-like receptor ligand are described. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films can include at least one designed peptide that includes one or more polypeptide epitopes from a virus, bacteria, fungus or parasite.
1. A composition comprising
a first multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the polyelectrolyte layers in the multilayer film comprises a first antigenic polyelectrolyte, wherein the first antigenic polyelectrolyte comprises a covalently linked viral, bacterial, fungal or parasite epitope,
wherein the multilayer film comprises a toll-like receptor ligand (TLR ligand) covalently linked to the first antigenic polyelectrolyte, wherein the TLR ligand is a lipoprotein or a lipopeptide, and
wherein the polyelectrolytes in the multilayer film comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.
2. The composition of claim 1 wherein the first antigenic polyelectrolyte is a polypeptide.
3. The composition of claim 1 , wherein the first multilayer film is deposited on a core particle.
4. The composition of claim 1 , further comprising a second multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the layers in the second multilayer film comprises a second antigenic polyelectrolyte,
wherein the second antigenic polyelectrolyte comprises a viral, bacterial, fungal or parasite polypeptide epitope, wherein the first and second antigenic polyelectrolytes comprise different polypeptide epitopes from the same or different organisms.
5. The composition of claim 4 , wherein the first and second antigenic polyelectrolytes are polypeptides.
6. The composition of claim 5 , wherein the first and second multilayer films are deposited onto core particles.
7. The composition of claim 1 , wherein the TLR ligand binds TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8 or TLR-9.
8. The composition of claim 1 , wherein the TLR ligand is N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam 3 Cys),[S-[2,3-bis(palmitoyloxy)propyl]cysteine] (Pam 2 Cys), monophospholipid A, imiquimod, or a combination thereof.
9. The composition of claim 1 , wherein the first polyelectrolyte is a polypeptide and the N-palmitoyl-S-[2,3-bis(palmitoyloxy)propyl]cysteine is covalently linked to the polypeptide.
10. The composition of claim 1 , comprising two or more different TLR ligands.
11. The composition of claim 1 , wherein the multilayer film comprises a polypeptide polyelectrolyte and wherein the polypeptide is covalently crosslinked within the multilayer film.
12. The composition of claim 11 , wherein the covalent crosslinks are amide bonds involving amino acid side chain functional groups.