Anti-malaria compositions and methods
Multilayer films comprise polypeptide epitopes from Plasmodium falciparum , specifically a circumsporozoite T1, B or T* epitope. 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 Plasmodium protozoan.
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 polypeptide polyelectrolyte,
wherein the first antigenic polypeptide comprises a Plasmodium falciparum circumsporozoite T1BT* epitope covalently linked to one or two surface adsorption regions at the C-terminus and/or the N-terminus of the polypeptide, wherein at least one of the surface adsorption regions comprises eight negatively or positively charged amino acid residues,
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,
wherein the first multilayer film is deposited on a core nanoparticle or microparticle, or is in the form of a nanocapsule or microcapsule prepared by dissolving the core particle,
wherein the first multilayer film retains more than half of its polyelectrolytes when incubated in phosphate buffered saline at 37° C. for 24 hours.
2. The composition of claim 1 , wherein the first multilayer film further comprises a TLR ligand.
3. The composition of claim 2 , wherein the TLR ligand is covalently linked to the first antigenic polypeptide.
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 Plasmodium falciparum circumsporozoite T1, B or T* epitope covalently linked to a second polyelectrolyte, wherein the first and second antigenic polyelectrolytes comprise different Plasmodium falciparum circumsporozoite epitopes.
5. The composition of claim 4 , wherein the first and second polyelectrolytes are polypeptides.
6. The composition of claim 4 , wherein the first and second multilayer films are deposited onto core particles.
7. The composition of claim 4 , wherein the first and/or the second multilayer film further comprises a TLR ligand.
8. The composition of claim 7 , wherein the TLR ligand is covalently linked to the first and/or second antigenic polyelectrolyte.
9. The composition of claim 4 , further comprising a third multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one of the layers in the third multilayer film comprises a third antigenic polyelectrolyte,
wherein the third antigenic polyelectrolyte comprises a Plasmodium falciparum circumsporozoite T1, B or T* epitope covalently linked to a third polyelectrolyte, wherein the first, second and third antigenic polyelectrolytes comprise different Plasmodium falciparum circumsporozoite epitopes.
10. The composition of claim 9 , wherein the first, second, and third polyelectrolytes are polypeptides.
11. The composition of claim 9 , wherein the first, second, and third multilayer films are deposited onto core particles.
12. The composition of claim 9 , wherein the first, second and/or third multilayer film further comprises a TLR ligand.
13. The composition of claim 12 , wherein the TLR ligand is covalently linked to the first, second and/or third antigenic polyelectrolyte.
14. A method of eliciting an immune response in a vertebrate organism comprising administering into the vertebrate organism the composition of claim 1 .
15. The composition of claim 1 , wherein the multilayer film is covalently crosslinked.
16. The composition of claim 15 , wherein the covalent crosslinks are amide bonds involving amino acid side chain functional groups.
17. The composition of claim 1 , wherein the first antigenic polypeptide has a magnitude of net charge per residue of greater than or equal to 0.2 at pH 7.0.
18. The composition of claim 1 , wherein the composition provides >90% reduction of PfPb ( Plasmodium bergheii transfected with the circumsporozoite gene of P. falciparum ) parasite rRNA levels in HepG2 cells measured by qPCR in a transgenic sporozoite neutralization assay (TSNA) performed on a 1:5 dilution of serum from C57BL/6J or BALB/c mice immunized on days 0, 21, and 42 with the composition, wherein the serum is harvested on day 49.
19. The composition of claim 1 , wherein the composition produces T1BT*-specific IgG titers, a specific CD4+ T-cell response, or both, in BALB/c or C57BL/6 mice immunized with the compositions.