Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) virus-like particles comprising heterologous antigens inserted into the envelope protein
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Publication Number
US-11345726-B2
Publication Date
2022-05-31
Expiration Date
Abstract
The present invention provides a particle comprising a polypeptide and at least one antigen, and a composition comprising thereof.
Core Innovation
The invention relates to a Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) virus-like particle that is capable of being self-assembled. The virus-like particle comprises capsid and envelope proteins, and the envelope protein has at least one antigen inserted therein.
The antigen is linked to the polypeptide or particle by an attachment site, by direct fusion, with optional peptide linkers or chemical cross-linkers. The spatial distance between the N-terminal residue and the C-terminal residue of the antigen is 30 Å or less, with further lower-distance ranges also described.
The document defines antigenic targets including T-cell receptor (TCR), MHC class I, MHC class II, T-cell epitopes, and B-cell epitopes, and also includes cytokines, tumor and self antigens, and epitopes, including antigen component forms. It further specifies antigen choices such as polypeptides derived from TNF-α, CD20, and CTLA4.
Claims Coverage
The independent claim set is grounded in a self-assembled CHIKV or VEEV virus-like particle with capsid and envelope proteins, an antigen incorporated in the envelope protein, and a defined spatial constraint between the antigen N- and C-terminal residues, yielding three primary inventive features across the independent claim(s).
Self-assembled CHIKV or VEEV virus-like particle comprising capsid and envelope proteins
A Chikungunya virus (CHIKV) or Venezuelan equine encephalitis virus (VEEV) virus-like particle capable of being self-assembled, comprising capsid and envelope proteins.
Envelope protein containing at least one antigen inserted therein
A virus-like particle wherein said virus-like particle comprises a CHIKV or VEEV envelope protein with at least one antigen inserted therein.
Spatial distance constraint between antigen N- and C-terminal residues
A virus-like particle wherein the spatial distance between the N-terminal residue and the C-terminal residue of the antigen is 30 Å or less.
Across the independent claim(s), the coverage is centered on a self-assembled CHIKV or VEEV virus-like particle with capsid and envelope proteins, an envelope protein bearing at least one inserted antigen, and a structural constraint that the antigen N-terminal-to-C-terminal spatial distance is 30 Å or less.
Stated Advantages
Demonstrates the ability to overcome self-antigen tolerance, supported by example antibody responses induced by VLPs.
Induces anti-TNF-α antibodies and anti-CD20 antibodies in mice in the examples.
Documented Applications
Immunological and therapeutic applications.
Autoimmune disease.
Cancer.
Macrophage antigen presentation.
Use of CHIKV and/or VEEV virus-like particles presenting antigens, as evidenced by induction of anti-TNF-α antibodies and anti-CD20 antibodies in mice, including in the context of overcoming self-antigen tolerance.
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