Chimeric adenoviral vectors
Inventors
Assignees
Publication Number
US-8222224-B2
Publication Date
2012-07-17
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 invention provides chimeric adenoviral vectors that incorporate nucleic acids encoding a heterologous polypeptide and a nucleic acid encoding a Toll-like receptor 3 (TLR-3) agonist, such as double-stranded RNA. These vectors are designed to be used in immunogenic compositions and can be administered non-parenterally, including routes such as oral, intranasal, or mucosal, to elicit an immune response specifically directed against the encoded heterologous polypeptide.
Chimeric adenoviral vectors of this invention utilize expression cassettes composed of at least two promoters: one linked to a nucleic acid encoding a TLR-3 agonist (e.g., dsRNA) and a second promoter linked to a nucleic acid encoding a heterologous polypeptide. This configuration allows for either the same or different promoters, with options including the beta actin promoter and cytomegalovirus (CMV) promoter. These compositions can be tailored to express viral, bacterial, fungal, parasite, or cancer antigens to generate antigen-specific humoral and/or cellular immune responses.
The problem addressed by this invention is the low efficiency of antigen-specific immune responses following administration of existing adenoviral vectors for nucleic acid-based vaccination. Prior systems resulted in suboptimal immune activation, especially when delivered by non-invasive routes. The new chimeric vectors overcome this by combining the immune-enhancing effects of a TLR-3 agonist with the antigen delivery system of adenoviral vectors, thus satisfying the medical need for more efficient and predictable immunogenic responses in vaccine development.
Claims Coverage
The patent claims cover two independent inventive features relating to methods for eliciting an immune response using chimeric viral vectors and immunogenic compositions.
Method for eliciting an immune response using a chimeric viral vector with a non-specific immune response enhancer
This inventive feature involves a method of eliciting an immune response by administering an immunogenic composition to a mammalian subject. The composition comprises: - A chimeric viral vector with a first promoter operably linked to a nucleic acid encoding a heterologous polypeptide. - A non-specific immune response enhancer selected from double-stranded RNA (dsRNA) and dsRNA mimetics. - A pharmaceutically acceptable carrier. The immune response is directed against the heterologous polypeptide. The route of administration is specifically selected from oral, intranasal, and mucosal routes.
Method for eliciting an immune response using a chimeric adenoviral expression vector encoding both a TLR-3 agonist and a heterologous polypeptide
This inventive feature covers a method of eliciting an immune response by administering an immunogenic composition to a mammalian subject. The composition includes: - A chimeric adenoviral expression vector containing a first promoter operably linked to a nucleic acid encoding a TLR-3 agonist, where the TLR-3 agonist is double-stranded RNA (dsRNA). - A second promoter operably linked to a nucleic acid encoding a heterologous polypeptide. - A pharmaceutically acceptable carrier. The immune response is directed against the heterologous polypeptide, and the administration route specified is oral.
The inventive features claimed focus on methods employing chimeric adenoviral vectors or viral vectors that encode both a heterologous antigen and an immune response enhancer (e.g., dsRNA), and their use in immunogenic compositions delivered by non-parenteral routes to elicit an antigen-specific immune response.
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.
The addition of a TLR-3 agonist significantly improves antigen-specific humoral and cellular immune responses compared to standard adenoviral vectors.
The approach allows for rapid, predictable, and inexpensive manufacture of vaccines with the same techniques, requiring only a change in the nucleic acid encoding the antigen of interest.
The compositions and methods enable high antibody titers and robust T cell responses upon oral, intranasal, or mucosal administration, outperforming existing vectors in non-parenteral delivery.
Documented Applications
Elicitation of antigen-specific immune responses in mammals against viral, bacterial, fungal, parasite, or cancer antigens using oral, intranasal, or mucosal administration.
Prevention or treatment of diseases such as viral infections (e.g., HIV, influenza, hepatitis), bacterial infections, parasitic infections, fungal infections, or cancer in warm-blooded animals, including humans.
Use in immunotherapy for stimulating the endogenous host immune system to react against tumors or infected cells.
Rapid development and production of nucleic acid-based vaccines by changing only the nucleic acid encoding the antigen of interest.
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