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Publication Number
US-10588954-B2
Publication Date
2020-03-17
Expiration Date
Abstract
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.
Core Innovation
The invention relates to anti-malaria multilayer film vaccine compositions and methods for eliciting an immune response in a vertebrate organism. The composition comprises a multilayer film comprising a plurality of oppositely charged polyelectrolyte layers in which one polyelectrolyte layer is an antigenic polyelectrolyte containing a modified Plasmodium falciparum circumsporozoite T* epitope, specifically the modified T* epitope of SEQ ID NO:5. The polyelectrolytes comprise a polycationic material or a polyanionic material having a molecular weight greater than 1,000 and at least 5 charges per molecule.
The multilayer film framework uses designed polypeptides with charged surface adsorption regions suitable for adsorption-based multilayer film formation using oppositely charged polyelectrolyte layers. The designed antigenic polyelectrolyte includes surface adsorption regions at the C-terminus and/or N-terminus, including regions having five or more negatively or positively charged amino acid residues.
The document further describes covalent linkage and covalent cross-linking options, including covalent cross-links that form amide bonds. It also describes use of modified cysteine-containing T* and T1BT* variants and addresses storage-related cysteine oxidation and disulfide dimerization.
Specific T* substitutions affect immune responses and protection, including a Cys→Ser substitution that retains or improves immune responses and a Cys→Ala substitution that reduces T-cell responses and protection. Cross-linking is described as increasing potency, and the multilayer film can optionally include a toll-like receptor ligand such as Pam3Cys, with multilayer-coated core particles for deposition also described.
Claims Coverage
The independent claim is directed to administering a multilayer film composition to elicit an immune response in a vertebrate organism. Across the presented claims, five inventive features are defined, with dependent claims refining the antigenic polyelectrolyte, polyelectrolyte structure, covalent cross-linking, toll-like receptor ligand inclusion, and terminal surface adsorption-region charge architecture.
Multilayer film immune-response method with modified Pf T* antigenic polyelectrolyte
A method of eliciting an immune response in a vertebrate organism by administering a composition comprising a multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, wherein one polyelectrolyte layer comprises a first antigenic polyelectrolyte that comprises a modified Plasmodium falciparum circumsporozoite T* epitope of SEQ ID NO:5, and wherein the polyelectrolytes comprise a polycationic material or a polyanionic material having a molecular weight of greater than 1,000 and at least 5 charges per molecule.
Covalently cross-linked base layers in the multilayer film
At least two polyelectrolyte layers of the multilayer film, excluding the layer containing the first antigenic polyelectrolyte, are covalently cross-linked.
Amide bond covalent cross-links formed from amino acid side chain functional groups
The covalent cross-links are specified as amide bonds formed using amino acid side chain functional groups.
Multilayer film including a toll-like receptor ligand
The multilayer film includes a toll-like receptor ligand.
Terminal surface adsorption regions with charged amino acid residue requirements
The first antigenic polyelectrolyte has one or two surface adsorption regions at the C-terminus and/or N-terminus, where at least one region contains five or more negatively or positively charged amino acid residues.
Across the claims, the core inventive concept is administering a composition containing a multilayer film of oppositely charged polyelectrolyte layers, with one layer comprising a first antigenic polyelectrolyte containing the modified Plasmodium falciparum circumsporozoite T* epitope of SEQ ID NO:5, using polyelectrolytes with defined molecular weight and charge per molecule. Dependent claims further introduce covalent cross-linking, optional toll-like receptor ligand inclusion, and terminal surface adsorption regions with minimum charged residue requirements.
Stated Advantages
Cross-linking increases potency.
Cysteine-containing T1BT* peptides are prone to oxidation and disulfide dimerization during storage, while serine variants show improved stability.
A Cys→Ser substitution retains or improves immune responses, whereas a Cys→Ala substitution reduces T-cell responses and protection.
Documented Applications
No documented applications found
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