Chimeric adenoviral vectors
Inventors
Assignees
Publication Number
US-8999946-B2
Publication Date
2015-04-07
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 contain nucleic acids encoding a heterologous polypeptide and a Toll-like receptor 3 (TLR-3) agonist, along with methods for using these vectors to elicit an immune response against an antigen of interest. One embodiment features vectors with two promoters: one driving expression of a TLR-3 agonist (such as dsRNA), and the other driving expression of the heterologous polypeptide. Immunogenic compositions containing these vectors can be administered to mammals via non-parenteral routes such as oral, intranasal, or mucosal delivery.
The invention addresses the problem that, although replication-incompetent adenoviral vectors are efficient for creating nucleic acid-based vaccines, their ability to generate a robust antigen-specific immune response is relatively low with current systems. This creates the need for improved adenoviral vectors that can efficiently stimulate immune responses to target antigens. The invention meets this need by incorporating TLR-3 agonists, which serve as immune response enhancers and act as adjuvants to improve the potency and specificity of immune responses elicited by adenoviral vectors.
An important aspect of the invention is the ability to use various promoters (e.g., CMV or beta actin promoters) to control the expression of both the TLR-3 agonist and the heterologous polypeptide within the chimeric adenoviral vector. The invention encompasses nucleic acids, vectors, and compositions that allow for rapid construction and administration of vaccine candidates against a wide range of diseases, including viral, bacterial, and cancer indications, by producing a strong and targeted immune response.
Claims Coverage
The claims contain two independent claims, each defining distinct inventive features relating to immunogenic compositions and methods for eliciting immune responses using chimeric adenoviral vectors.
Immunogenic composition containing a chimeric adenoviral vector with a heterologous polypeptide and a non-specific immune response enhancer
This inventive feature covers an immunogenic composition comprising: - A chimeric adenoviral expression vector containing a promoter operably linked to a nucleic acid encoding a heterologous polypeptide, where the heterologous polypeptide is either a human papilloma virus (HPV) polypeptide or herpes simplex virus (HSV) polypeptide. - A non-specific immune response enhancer selected from dsRNA and a dsRNA mimetic. - A pharmaceutically acceptable carrier.
Method for eliciting an immune response using a chimeric adenoviral vector and a non-specific immune response enhancer
This inventive feature is a method for eliciting an immune response by administering to a mammalian subject: - A chimeric adenoviral expression vector with a promoter operably linked to a nucleic acid encoding a heterologous polypeptide, where the heterologous polypeptide is an HPV polypeptide or HSV polypeptide. - A non-specific immune response enhancer selected from dsRNA and a dsRNA mimetic, such that the immune response is directed against the heterologous polypeptide.
These inventive features define compositions and methods that employ chimeric adenoviral vectors combined with dsRNA or dsRNA mimetics as immune response enhancers to target HPV or HSV polypeptides, aiming to elicit effective antigen-specific immune responses.
Stated Advantages
The chimeric adenoviral vectors of the invention elicit strong and effective immune responses specific for the heterologous polypeptide, particularly when administered via a non-parenteral route.
The use of a TLR-3 agonist as an adjuvant greatly improves adenovirus-mediated antibody and cellular immune responses to antigens of interest after administration of the chimeric vector.
The invention allows for rapid, predictable, and inexpensive manufacturing of nucleic acid-based vaccines by using interchangeable nucleic acids encoding the selected antigen.
The approach enables effective oral, intranasal, or mucosal delivery of immunogenic compositions, providing flexibility and increased accessibility for vaccine administration.
Documented Applications
Use of immunogenic compositions to elicit antigen-specific immune responses for treatment or prevention of diseases such as viral infections (including HIV, hepatitis, HPV, HSV), bacterial infections, parasitic infections, fungal infections, or cancer.
Application of compositions as vaccines for prophylactic or therapeutic purposes in mammals, including humans.
Administration of chimeric adenoviral vectors for oral, intranasal, or mucosal immunization to generate targeted immune responses to specific antigens.
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