Chimeric adenoviral vectors
Inventors
Assignees
Publication Number
US-7879602-B2
Publication Date
2011-02-01
Expiration Date
2027-02-28
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Abstract
The present invention provides chimeric adenoviral vectors and methods for using the vectors to elicit an immune response to an antigen of interest.
Core Innovation
The present invention provides chimeric adenoviral vectors that include nucleic acids encoding a heterologous polypeptide and a nucleic acid encoding a TLR-3 agonist, specifically a double-stranded RNA (dsRNA). The invention also describes immunogenic compositions containing these vectors and methods to elicit an immune response against the heterologous polypeptide by administering an immunogenically effective amount of the composition to a mammalian subject. The chimeric adenoviral vectors utilize separate promoters for the heterologous polypeptide and the TLR-3 agonist, enhancing the expression of both components.
The problem addressed by this invention is the low efficiency of antigen-specific immune responses elicited by adenoviral vectors known in the art. While nucleic acid-based vaccines offer advantages such as rapid and consistent manufacturing, existing adenovirus vectors are limited by their inability to efficiently generate strong immune responses against target antigens. The patent seeks to overcome these limitations by incorporating TLR-3 agonists into adenoviral vectors to act as adjuvants and significantly improve immunogenicity.
The invention further enables non-parenteral administration routes, such as oral, intranasal, or mucosal, which facilitate efficient delivery and immune response induction at mucosal surfaces. The chimeric vectors can be tailored to encode a range of antigens, including viral, bacterial, fungal, parasitic, and cancer antigens, leveraging the adjuvant properties of encoded TLR-3 agonists to stimulate strong adaptive immune responses.
Claims Coverage
The patent includes three independent claims covering chimeric adenoviral expression vectors and methods for eliciting an immune response, each with distinct inventive features.
Chimeric adenoviral vector with dual promoters for TLR-3 agonist and heterologous polypeptide
A chimeric adenoviral expression vector comprising: - An expression cassette with a first promoter operably linked to a nucleic acid encoding a TLR-3 agonist, wherein the TLR-3 agonist is a double-stranded RNA (dsRNA). - A second promoter operably linked to a nucleic acid encoding a heterologous polypeptide selected from influenza virus HA, influenza virus M1, influenza virus NP, HIV gag, and HIV env. This arrangement permits the co-expression of a dsRNA TLR-3 agonist and a clinically relevant antigenic polypeptide within a single adenoviral vector.
Chimeric adenoviral vector with TLR-3 agonist sequence choice
A chimeric adenoviral expression vector in which: - The TLR-3 agonist is a dsRNA, and the nucleic acid encoding the TLR-3 agonist comprises a sequence selected from SEQ ID NOS: 8, 9, 10, 11, and 12. - The vector includes a first promoter operably linked to the TLR-3 agonist and a second promoter operably linked to a heterologous polypeptide. This implementation enables specificity in the choice of sequence for the TLR-3 agonist component carried by the vector.
Method for eliciting immune response using chimeric adenoviral vector via non-parenteral routes
A method to elicit an immune response in a mammalian subject comprising: - Administering an immunogenically effective amount of a chimeric adenoviral expression vector comprising a first promoter operably linked to a nucleic acid encoding a dsRNA TLR-3 agonist and a second promoter operably linked to a nucleic acid encoding a heterologous polypeptide. - The immune response is directed against the heterologous polypeptide. - The administration route is selected from oral, intranasal, and mucosal. This method explicitly covers non-parenteral delivery routes for the novel chimeric vector to induce targeted immune responses.
The inventive features focus on the construction of adenoviral vectors with separate promoters for a dsRNA TLR-3 agonist and a heterologous antigen, use of specific SEQ ID NOs for TLR-3 agonists, and methods for non-parenteral administration to elicit immune responses.
Stated Advantages
The chimeric adenoviral vectors elicit strong and effective immune responses specific for the heterologous polypeptide, particularly when administered via a non-parenteral route.
Administration of dsRNA TLR-3 agonists as adjuvants in conjunction with viral vectors significantly improves the antigen-specific immune response.
Most nucleic acid-based vaccines using these vectors can be manufactured rapidly and efficiently by altering only the nucleic acid encoding the antigen of interest.
The chimeric adenoviral vectors enable efficient induction of both humoral and cell-mediated immune responses when compared to standard adenoviral vectors.
Versatile application allows expression of a range of clinically relevant antigens for prevention or treatment of a variety of diseases and disorders.
Documented Applications
Eliciting an antigen-specific immune response in warm-blooded animals, including humans, rodents (mouse, rat, guinea pig), and primates (chimpanzee, rhesus macaque), using chimeric adenoviral vectors via oral, intranasal, or mucosal administration.
Therapeutic and prophylactic use for the prevention and treatment of diseases such as viral infections, bacterial infections, parasitic infections, fungal infections, and cancer by expressing clinically relevant antigens.
Induction of anti-tumor, anti-viral, or antibacterial immune responses by generating antibodies or cytolytic T cells against tumor cells, virally infected cells, or bacterially infected cells.
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