Anti-malaria compositions and methods
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9433671-B2
Publication Date
2016-09-06
Expiration Date
Abstract
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.
Core Innovation
The invention relates to anti-malaria vaccine compositions comprising multilayer films made of a plurality of oppositely charged polyelectrolyte layers. One polyelectrolyte layer includes a first antigenic polypeptide polyelectrolyte in which a Plasmodium falciparum circumsporozoite T1BT* epitope is covalently linked to one or two surface adsorption regions at the C-terminus and/or the N-terminus of the polypeptide, and at least one surface adsorption region comprises eight negatively or positively charged amino acid residues.
The polyelectrolyte layers comprise polycationic and/or polyanionic materials having a molecular weight of greater than 1,000 and at least 5 charges per molecule. 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, and the multilayer film retains more than half of its polyelectrolytes after incubation in phosphate buffered saline at 37°C for 24 hours.
The described approach addresses the problem of developing effective anti-malaria vaccine compositions associated with Plasmodium falciparum circumsporozoite epitopes and their immune responses. The document further describes incorporation of Toll-like receptor ligands within the immunogenic composition, including cases where the TLR ligands are covalently attached to antigenic polypeptides or are co-/pre-deposited, and also includes stability and design constraints for designed polypeptides and immunological performance readouts including antibody titers and T-cell IFNγ/IL-5 responses.
Claims Coverage
This family centers on a composition defined by a multilayer film of oppositely charged polyelectrolytes deposited on a core particle or present as nano-/microcapsules. The claim set specifies an antigenic polypeptide polyelectrolyte bearing a Plasmodium falciparum circumsporozoite T1BT* epitope covalently linked to charged surface adsorption regions, defined polyelectrolyte charge and molecular-weight parameters, and a PBS/37°C/24-hour retention requirement. Dependent claims further add inventive constraints for immune-modulating components, additional antigenic layers with different circumsporozoite epitopes, covalent crosslinking, quantitative biophysical constraints, and a quantitative efficacy target measured via a defined PfPb/qPCR readout.
Oppositely charged polyelectrolyte multilayer film on a core particle or in nano-/microcapsule form
A composition comprising a first multilayer film comprising a plurality of oppositely charged polyelectrolyte layers, where 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.
Plasmodium falciparum circumsporozoite T1BT* covalently linked to charged surface adsorption regions
One polyelectrolyte layer comprises a first antigenic polypeptide polyelectrolyte in which a Plasmodium falciparum circumsporozoite T1BT* epitope is covalently linked to one or two surface adsorption regions at the C-terminus and/or the N-terminus of the polypeptide, with at least one surface adsorption region comprising eight negatively or positively charged amino acid residues.
Polycationic or polyanionic polyelectrolytes with defined molecular weight and charge density
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.
Multilayer film polyelectrolyte retention in phosphate buffered saline at 37°C for 24 hours
The first multilayer film retains more than half of its polyelectrolytes when incubated in phosphate buffered saline at 37°C for 24 hours.
TLR ligand in the multilayer film
The first multilayer film includes a TLR ligand.
Multiple multilayer films presenting different Plasmodium falciparum circumsporozoite epitopes
The composition includes an additional multilayer film in which one layer carries a second antigenic polyelectrolyte containing a covalently linked Plasmodium falciparum circumsporozoite T1, B, or T* epitope, where the first and second antigenic polyelectrolytes present different Plasmodium falciparum circumsporozoite epitopes.
Covalent crosslinking of the multilayer film
The multilayer film is covalently crosslinked.
Net charge per residue constraint at pH 7.0 for the first antigenic polypeptide
The first antigenic polypeptide has a net charge per residue of at least 0.2 at pH 7.0.
Quantified PfPb reduction in HepG2 cells using qPCR in a transgenic sporozoite neutralization assay
The composition provides more than 90% reduction of PfPb parasite rRNA levels in HepG2 cells as measured by qPCR in a transgenic sporozoite neutralization assay (TSNA).
Overall, the claim coverage is anchored on an oppositely charged polyelectrolyte multilayer film configured with a Plasmodium falciparum circumsporozoite T1BT* epitope covalently linked to charged adsorption regions, defined polyelectrolyte charge/molecular-weight properties, and an explicit PBS/37°C/24-hour retention requirement. Dependent claims add immune modulation via TLR ligands, additional multilayer films bearing different circumsporozoite epitopes, covalent crosslinking, a net charge per residue constraint at pH 7.0, and a quantitative >90% PfPb rRNA reduction criterion measured in a defined TSNA/qPCR context.
Stated Advantages
Provides more than 90% reduction of PfPb parasite rRNA levels in HepG2 cells as measured by qPCR in a transgenic sporozoite neutralization assay (TSNA).
The first multilayer film retains more than half of its polyelectrolytes when incubated in phosphate buffered saline at 37°C for 24 hours.
Documented Applications
Anti-malaria prevention vaccine compositions featuring Plasmodium falciparum circumsporozoite T1BT* epitopes delivered as polyelectrolyte multilayer films/microparticles/nanoparticles/nano-/microcapsules, with immune response evaluation including antibody titers and T-cell IFNγ/IL-5 responses.
Interested in licensing this patent?