Respiratory syncytial virus antigenic compositions and methods

Inventors

Powell, Thomas J. • Boyd, James Gorham

Assignees

Targeted Nano Technologies LLC

Abstract

Multilayer films comprise polypeptide epitopes from RSV. The multilayer films are capable of eliciting an immune response in a host upon administration to the host. The multilayer films include at least one designed peptide that includes one or more polypeptide epitopes from RSV. Specifically, the multilayer films include two polypeptide epitopes from RSV, such as an epitope that elicits a specific T-cell response such as a cytotoxic T-cell response, and an epitope that elicits a specific antibody response.

Core Innovation

The invention relates to a composition comprising particles containing RSV epitopes, where the particles comprise an RSV-M2 peptide epitope and an RSV-G peptide epitope. The RSV-M2 and RSV-G peptide epitopes are covalently linked to one or more surface adsorption regions, or covalently linked to a same surface adsorption region, to form one or more designed polypeptides, and the designed polypeptides are placed in one or more layers of the same multilayer film. The epitopes do not require full-length RSV-M2 or full-length RSV-G.

The disclosed particles include multilayer film deposition on a core particle or formation of a hollow particle, with the multilayer film comprising two or more layers of polyelectrolytes. Adjacent multilayer film layers comprise oppositely charged polyelectrolytes, where the polyelectrolyte is a polycationic material or a polyanionic material having a molecular weight greater than 1,000 and at least 5 charges per molecule. Surface adsorption regions contain at least eight amino acid residues and have the same sign of charge as the designed polypeptide, enabling covalent linkage at the adsorption region level within the multilayer architecture.

The invention also addresses the use of RSV-M2 and RSV-G epitopes in the same or different ELBL multilayer films while maintaining an overall multilayer film design based on alternating oppositely charged polyelectrolyte layers. The summary further states unexpected improved immune potency from combining RSV-G (antibody) and RSV-M2 (T-cell) epitopes in the same or different ELBL multilayer films.

The described particle architecture includes core particle structures, including coated or hollow multilayer shells using core particles such as CaCO3. The summary further states multilayer stabilization approaches including disulfide "clocking" or amide covalent crosslinking, and discusses designed polypeptide constraints for length and net charge thresholds.

Claims Coverage

The patent includes one independent claim that covers a composition of particles containing both an RSV-M2 peptide epitope and an RSV-G peptide epitope presented via designed polypeptides covalently linked to surface adsorption regions within the same multilayer film, with deposition on a core particle or formation of a hollow particle. Dependent claims further refine designed polypeptide parameters and add constraints on multilayer crosslinking chemistry, including amide bond cross-linking.

Overall, claim coverage centers on particles bearing a multilayer film with engineered, epitope-bearing designed polypeptides covalently linked to surface adsorption regions and presented in layers of an ELBL-style polyelectrolyte multilayer with charge-sign matching and specified polyelectrolyte charge density, with the multilayer film supported on core particles or formed as hollow particles. Dependent claims further narrow designed polypeptide length/charge and constrain multilayer cross-linking through amide bonds.

Stated Advantages

Documented Applications