MHC class i associated peptides for prevention and treatment of multiple flavi virus

Inventors

Philip, Ramila

Assignees

Emergex Vaccines Holding Ltd

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Publication Number

US-12178867-B2

Patent

Publication Date

2024-12-31

Expiration Date


Abstract

The invention provides a vaccine composition comprising a flavi peptide comprising one or more CD8+ T cell epitopes.

Core Innovation

The invention relates to a vaccine composition that comprises a conjugate in which a flavivirus peptide is attached to a gold nanoparticle. The flavivirus peptide is 8 to 30 amino acids in length and comprises a CD8+ T cell epitope set forth in SEQ ID NO: 15 or SEQ ID NO: 18, or a variant that differs by one amino acid substitution, deletion or insertion. This conjugate format presents CD8+ T cell epitopes through MHC class I to drive CTL responses.

The gold nanoparticle is coated with galactose and/or GlcNAc. The document emphasizes conserved CD8+ T cell epitopes and epitope variants for prevention and/or treatment across multiple flaviviruses, including Zika, Dengue and West Nile virus, with additional examples including yellow fever virus and Japanese encephalitis virus. Variants are described as retaining relevant features for cross-reactivity.

The described approach expands the vaccine concept beyond a single peptide by using multiple epitopes, including epitope sets from SEQ ID NOs: 1-23. It also describes peptide and polynucleotide (DNA/RNA/mRNA) vaccine options and additional immune components including CD4+ and B cell epitopes. The document further describes diagnostic and CTL-generation aspects grounded in immunoproteomics-derived epitope discovery and CTL assay figure summaries.

Claims Coverage

The independent claim covers a specific vaccine composition built on a flavivirus peptide-gold nanoparticle conjugate with defined CD8+ epitope sequence constraints and specific galactose/GlcNAc nanoparticle coatings. Across the claim family, additional constraints refine epitope selection, nanoparticle coating stereochemistry, conjugate linking architecture, and administration and use for immune modulation and/or infection prevention or treatment.

Conjugate with flavivirus CD8+ T cell epitope attached to galactose/GlcNAc-coated gold nanoparticle

A vaccine composition comprising a conjugate, the conjugate comprising a flavivirus peptide attached to a gold nanoparticle, wherein the flavivirus peptide is 8 to 30 amino acids in length and comprises a CD8+ T cell epitope comprising the amino acid sequence set forth in SEQ ID NO: 15 or SEQ ID NO: 18, or a variant thereof which differs from SEQ ID NO: 15 or SEQ ID NO: 18 by one amino acid substitution, deletion or insertion; and the gold nanoparticle is coated with galactose and/or GlcNAc.

Claim coverage centers on a flavivirus peptide-gold nanoparticle conjugate for presenting CD8+ T cell epitopes, with peptide length and epitope sequence or variant limits and with galactose/GlcNAc-coated gold nanoparticles. Dependent claims further narrow epitope selection, specify sugar stereochemistry, constrain linker structure, and refine administration route.

Stated Advantages

Reduced adverse reactions.

Cross-protection across flaviviruses, lineages and serotypes.

Coverage across HLA supertypes using multiple epitopes.

Avoidance of live virus and/or traditional adjuvants.

Documented Applications

Prevention and/or treatment of flavivirus infection via CTL responses driven by CD8+ T cell epitopes presented through MHC class I.

Diagnostic and CTL-generation approaches grounded in immunoproteomics-derived epitope discovery and CTL assays.

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