Peptide vaccine formulations and use thereof for inducing an immune response
Inventors
SEDER, Robert • Lynn, Geoffrey
Assignees
US Department of Health and Human Services
Publication Number
US-11191821-B2
Publication Date
2021-12-07
Expiration Date
2037-02-27
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Embodiments of a novel platform for delivering a peptide antigen to a subject to induce an immune response to the peptide antigen are provided. For example, nanoparticle polyplexes are provided that comprise a polymer linked to a peptide conjugate by an electrostatic interaction. The conjugate comprises a peptide antigen linked to a peptide tag through an optional linker. An adjuvant may be included in the nanoparticle polyplex, linked to either the polymer or the conjugate, or admixed with the nanoparticles. The nanoparticle polyplex can be administered to a subject to induce an immune response to the peptide antigen.
Core Innovation
The invention relates to a novel platform for delivering peptide antigens to subjects in order to induce an immune response against those antigens. It involves the creation of immunogenic compositions comprising nanoparticle polyplexes formed by electrostatic interactions between a polymer and a peptide antigen conjugate. The conjugate includes a peptide antigen linked to a peptide tag through an optional linker. These nanoparticles may further include an adjuvant, which can be linked to the polymer or the conjugate or admixed within the nanoparticle complex. The nanoparticle polyplexes can enter immune cells under physiological conditions, thereby inducing an immune response to the peptide antigen in the subject.
The problem addressed is the difficulty of inducing effective immune responses to peptide antigens, particularly soluble peptide antigens, which have varied physical and chemical properties that make vaccine formulation unpredictable and produce variable immune responses. Previous cancer vaccine strategies using tumor-associated self-antigens have resulted in toxicity and morbidity, while peptide-based vaccines face challenges due to diversity in peptide solubility and charge leading to variability in immunogenicity. There is a need for a safe, scalable, and effective method that can reliably induce immune responses to diverse peptide neoantigens, especially in the context of personalized cancer vaccines.
The invention overcomes prior difficulties by providing immunogenic compositions where peptide antigens are formulated as peptide conjugates with charged tags that facilitate formation of nanoparticle polyplexes with polymers of opposite charge through electrostatic interactions. This particle formation can be combined with adjuvants, such as TLR-7/8 agonists, to co-deliver antigen and innate immune stimulants within the same nanoparticle structure, enhancing uptake by immune cells and improving the magnitude and durability of the immune response. This strategy allows soluble peptide antigens, which are otherwise weakly immunogenic, to be rendered more immunogenic by incorporating or inducing their assembly into nanoparticles, thereby broadening and enhancing T cell responses.
Claims Coverage
The claims cover an immunogenic composition comprising polymer nanoparticles formed by electrostatic interaction between polymers and peptide antigen conjugates, where the nanoparticles co-deliver adjuvants to induce an immune response.
Polymer nanoparticles comprising peptide antigen conjugates linked by electrostatic interaction
The composition includes polymer nanoparticles where a first polymer is linked to a peptide antigen conjugate by electrostatic interaction, forming polyplexes. The conjugate consists of a peptide antigen linked to a peptide tag.
Incorporation of adjuvants within nanoparticles
An adjuvant is included in the polymer nanoparticles, which may be linked to the conjugate or polymer, or be present in the nanoparticle complex to induce immune stimulation alongside antigen delivery.
Use of peptide tags with specific charge ratios
Peptide tags provide either net positive or negative charge; charge ratios between the polymer and conjugate are optimally controlled (from about 20:1 to 1:20 mol/mol, with preferred around 5:1) to form stable nanoparticles that promote immune responses.
Varied polymer chemistries and nanoparticle sizes
Polymers include poly(ethylenimine), poly(lysine), and poly(arginine) polymers. The polymer nanoparticles formed are from about 20 to about 200 nm in diameter, ensuring efficient uptake by immune cells.
Self-assembly of nanoparticle polyplexes in physiological buffer
The polymers linked to conjugates and adjuvants self-assemble into nanoparticles in phosphate buffered saline at pH 7.4, enabling stable compositions suitable for administration.
Method of inducing immune response through administration
A method is claimed for inducing an immune response to a peptide antigen in a subject by administering an effective amount of the polymer nanoparticle immunogenic composition.
The claims encompass compositions where charged polymer-peptide conjugate complexes form nanoparticles including adjuvants that can enter immune cells to induce immune responses, and methods of their use for vaccination purposes.
Stated Advantages
The compositions improve immunogenicity of peptide antigens, especially soluble peptide antigens, by forming nanoparticles that enhance uptake by immune cells and robust immune responses.
Co-delivery of peptide antigen and adjuvant ensures persistent innate immune stimulation and prevents tolerance.
Provides a chemically defined, scalable, and generalizable platform suitable for individualized cancer vaccines.
Particle formation enhances antigen presentation duration and magnitude of T cell responses leading to improved tumor clearance.
Documented Applications
Use as personalized cancer vaccines delivering patient-specific tumor neoantigens to induce tumor-specific T cell responses for tumor prevention and treatment.
Vaccination against infectious agents including viruses, bacteria, fungi, and protozoa by delivering peptide antigens from these pathogens.
Adjunctive use in combination with immune checkpoint inhibitors (e.g., anti-PD-1) to enhance anti-cancer T cell immunity.
Administration to subjects at risk for or having infectious diseases or cancer for prophylactic or therapeutic immune response induction.
Interested in licensing this patent?