Anti-malaria compositions and methods
Described herein are multilayer films that include modified polypeptide epitopes from Plasmodium falciparum , specifically a modified 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 the modified T* polypeptide epitope from a Plasmodium protozoan.
1. A method of eliciting an immune response in a vertebrate organism comprising administering into the vertebrate organism a composition comprising
a 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 modified Plasmodium falciparum circumsporozoite T* epitope of SEQ ID NO: 5, 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 method of claim 1 , wherein the multilayer film is deposited on a core nanoparticle or core microparticle, or is in the form of a nanocapsule or microcapsule prepared by dissolving the core nanoparticle or core microparticle.
3. The method of claim 1 , wherein the modified Plasmodium falciparum circumsporozoite T* epitope of SEQ ID NO: 5 is covalently linked to a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.
4. The method of claim 1 , wherein the first antigenic polyelectrolyte comprises one or two surface adsorption regions at the C-terminus and/or the N-terminus, wherein at least one of the surface adsorption regions comprises five or more negatively or positively charged amino acid residues.
5. The method of claim 1 , wherein the multilayer film further comprises a toll-like receptor ligand.
6. The method of claim 5 , wherein the toll-like receptor ligand is covalently linked to the first antigenic polyelectrolyte.
7. The method of claim 1 , wherein the first antigenic polyelectrolyte comprises a modified Plasmodium falciparum circumsporozoite T1BT* epitope of SEQ ID NO: 7.
8. The method of claim 7 , wherein the modified Plasmodium falciparum circumsporozoite T1BT* epitope of SEQ ID NO: 7 is covalently linked to a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.
9. The method of claim 7 , wherein the first antigenic polyelectrolyte comprises one or two surface adsorption regions at the C-terminus and/or the N-terminus, wherein at least one of the surface adsorption regions comprises five or more negatively or positively charged amino acid residues.
10. The method of claim 7 , wherein the first antigenic polypeptide is SEQ ID NO: 12 or SEQ ID NO: 13.
11. The method of claim 1 , wherein administration of the composition to a host organism produces an epitope-specific T-cell response, wherein the T-cell response is an IFNΥ T-cell response, an IL-5 T-cell response, or both.
12. The method of claim 1 , wherein at least two polyelectrolyte layers of the multilayer film, other than the layer containing the first antigenic polyelectrolyte, are covalently cross-linked.
13. The method of claim 12 , wherein the covalent cross-links are amide bonds involving amino acid side chain functional groups.