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Publication Number
US-9872899-B2
Publication Date
2018-01-23
Expiration Date
Abstract
Novel compositions useful as human rhinovirus immunogens are provided. The compositions enable a host response to sites normally not recognized by a host.
Core Innovation
The invention relates to immune refocusing of human rhinovirus immunogens by modifying immunodominant, strain-specific capsid epitopes to dampen their antigenicity so the immune system targets more conserved subdominant epitopes. The problem addressed is that immune responses to human rhinovirus immunogens preferentially target immunodominant, strain-specific epitopes rather than conserved subdominant epitopes, limiting breadth.
Immune dampening of those immunodominant capsid epitopes is used to enable broader targeting of subdominant epitopes associated with cross-protective immunity. The disclosed approach provides broad vaccine and antigen concepts independent of vector or delivery format, including recombinant subunit antigens, virus-like particles, and engineered recombinant viruses.
The sequences relate to epitope-containing polypeptides or virus formulations of human rhinovirus. The subject matter includes multiple human rhinovirus constructs and variants, including HRV39 Attn WT and HRV39 Attn M1 through HRV39 Attn M18, each associated with a corresponding SEQ ID NO.
Claims Coverage
The consolidated claim coverage identifies one independent claim and dependent refinements. The inventive features center on an epitope of human rhinovirus defined by specified amino acid sequences, with additional coverage for composition and delivery formats.
Epitope-defined polypeptide or human rhinovirus comprising specified amino acid sequences
A polypeptide or virus comprising an epitope of a human rhinovirus, wherein the epitope comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 16-33, 35, 37, 39, 41, 45, 47, 49, 65-73, 75-91 and 92.
Pharmaceutical composition comprising the epitope-defined polypeptide or virus
A pharmaceutical composition that includes the polypeptide or virus of the epitope-defined polypeptide or human rhinovirus comprising specified amino acid sequences.
Virus-like particle comprising the epitope-defined polypeptide
A virus-like particle comprising the polypeptide of the epitope-defined polypeptide or human rhinovirus comprising specified amino acid sequences.
Virus-like particle including a toxic or therapeutic molecule
The virus-like particle further includes a toxic or therapeutic molecule.
Immunogenic composition with selected adjuvant types
An immunogenic composition wherein the adjuvant is chosen from specified adjuvant types including an aluminum salt, a calcium salt, an iron salt, a zinc salt, an insoluble suspension of acylated tyrosine, acetylated sugars, cationically derived polysaccharides, anionically derived polysaccharides, and polyphosphazenes.
Overall, the claim set is anchored on an epitope of human rhinovirus defined by specified amino acid sequences and broadened through dependent claim coverage of composition, virus-like particle, toxic or therapeutic molecule, and adjuvant variants.
Stated Advantages
Enables broader immune targeting of conserved subdominant epitopes by dampening immunodominant, strain-specific capsid epitopes.
Supports development of cross-protective immunity.
Supports therapeutic and diagnostic antibody development, including mapping of antibody escape mutants and broader cross-neutralization against unmodified antigens.
Documented Applications
Vaccine and antigen development aimed at eliciting cross-protective immunity by immune refocusing of human rhinovirus immunogens toward conserved subdominant epitopes.
Therapeutic and diagnostic antibody applications, including antibody escape mutant mapping and assessment of cross-neutralization against heterologous human rhinovirus serotypes.
Use of immune refocusing human rhinovirus immunogens in recombinant subunit antigens, virus-like particles, and engineered recombinant viruses.
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