Baculovirus display vectors and uses thereof
Inventors
Chang, Chia-Jung • LIAO, Yan-Chiou • Chou, Wei-I • Chang, Hsiu-Kang
Assignees
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Publication Number
US-10172931-B2
Publication Date
2019-01-08
Expiration Date
Abstract
A recombinant baculovirus displaying on its envelop a fusion protein is disclosed. The fusion protein comprises a heterologous antigen, and a C-terminal region of baculovirus envelope GP64 protein, which has at least 100 amino acid residues in length and lacks a B12D5 binding epitope located within the central basic region of the GP64 protein. The genome of the recombinant baculovirus comprises a transgene encoding a fusion protein that comprises a signal peptide, the heterologous antigen, and the C-terminal region of the baculovirus envelope GP64 protein, in which the antigen is located between the signal peptide and the C-terminal region of the GP64 protein. Methods for eliciting an antigen-specific immunogenic response in a subject in need thereof are also disclosed.
Core Innovation
The patent discloses baculovirus display vectors in which a transgene encodes a fusion protein that is displayed on the envelope of a recombinant baculovirus. The fusion protein comprises an N-terminal signal peptide, a heterologous antigen, and a C-terminal region of baculovirus envelope GP64 protein, with the heterologous antigen positioned between the signal peptide and the GP64-derived C-terminal region.
The GP64 C-terminal region is defined as having at least 100 amino acid residues in length. The GP64 central basic region includes a B12D5 binding epitope, and the fusion protein is characterized by lacking that B12D5 binding epitope located within the central basic region. The B12D5 binding epitope is specified as comprising the amino acid sequence of SEQ ID NO: 2 or 3.
The patent further includes recombinant baculovirus displaying the described fusion protein on its envelope, and it uses the platform to elicit an antigen-specific immunogenic response. The disclosed antigen classes include pathogen antigens, cancer cell antigens, and immune checkpoint proteins such as PD-1, PD-L1, PD-L2, and CTLA-4. Documented examples include CSFV E2-gBac, PEDV S1-gBac, and hPD-1gBac, with antigen detection reported by Western blot.
Claims Coverage
Two independent claims are identified: a vector claim and a recombinant baculovirus displaying claim. Each claim is directed to an envelope-anchored fusion protein architecture that places a heterologous antigen between an N-terminal signal peptide and a modified GP64 C-terminal region lacking a specified B12D5 binding epitope. The inventive features include defining the GP64 C-terminal region length and epitope deletion, and specifying envelope display on a recombinant baculovirus.
Vector encoding a signal peptide–heterologous antigen–GP64 C-terminal fusion lacking a B12D5 epitope
A vector comprising a transgene encoding a fusion protein having an N-terminal signal peptide, a heterologous antigen, and a C-terminal region of baculovirus envelope GP64 protein with at least 100 amino acid residues that lacks a B12D5 binding epitope located within the central basic region, where the heterologous antigen is located between the signal peptide and the C-terminal region.
Recombinant baculovirus envelope display of a heterologous antigen–GP64 C-terminal fusion lacking a B12D5 epitope
A recombinant baculovirus displaying on its envelope a fusion protein comprising a heterologous antigen and a C-terminal region of baculovirus envelope GP64 protein having at least 100 amino acid residues and lacking a B12D5 binding epitope located within the GP64 central basic region.
Across the independent claims, the core inventive concept is the same: an envelope-anchored fusion protein architecture that places a heterologous antigen between an N-terminal signal peptide and a GP64-derived C-terminal region that is at least 100 amino acids long and lacks a B12D5 binding epitope within the GP64 central basic region. The vector claim focuses on a transgene-containing vector, while the second independent claim focuses on a recombinant baculovirus that displays the fusion protein on its envelope.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Eliciting an antigen-specific immunogenic response in a subject in need thereof by administering a therapeutically effective amount of the recombinant baculovirus.
Displaying example antigens for immune-related targets and pathogen/cancer targets, including CSFV E2-gBac, PEDV S1-gBac, and hPD-1gBac, with antigen detection reported by Western blot.
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