Vaccine delivery systems using yeast cell wall particles
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Abstract
The present invention generally relates to compositions and methods for delivering a vaccine. The compositions and methods disclosed herein are particularly useful in making prophylactic and therapeutic vaccines.
Core Innovation
A composition is described for vaccine delivery that includes a yeast cell wall particle (YCWP) modified by capping or coating with a silicate and loaded with an exogenous biological material. The exogenous biological material comprises a protein or a fragment thereof, nucleic acid, carbohydrate, antigen, or a combination thereof, and the described approach excludes tumor lysate, viral antigen, and bacterial antigen as the loaded biological material.
The silicate comprises an orthosilicate having an organic moiety attached to each of four oxygen compounds, with specific embodiments including tetraalkylorthosilicates such as tetraethylorthosilicate (TEOS), tetramethylorthosilicate, tetrapropylorthosilicate, and tetrabutylorthosilicate. The described rationale is that silicate capping improves retention of the loaded material and improves delivery or release into the cytoplasm after phagocytosis.
The document describes prophylactic and therapeutic use of the composition, including delivery to dermal or monocytic/phagocytic cells and use involving phagocytosis. It also describes an optional ex vivo incubation of the silicate-capped, loaded YCWP with isolated immature dendritic cells prior to administration, and reports enhanced immunogenic responses versus uncapped YCWPs.
In the examples, the silicate-capped YCWPs are loaded with tumor lysate and used in assays including leaking or phagocytosis assays and an in vivo mouse survival study. The described results indicate improved survival for silicate-capped tumor-lysate loaded YCWPs, particularly when adjuvants are included, relative to uncapped YCWPs.
Claims Coverage
The partial claim set includes two independent composition claims. The inventive features are centered on silicate capping or coating of YCWP combined with loading a specified class of exogenous biological material, with orthosilicate structure required in one independent claim.
Silicate-capped yeast cell wall particle composition with non-tumor-lysate exogenous biological material
A composition comprising a yeast cell wall particle (YCWP), a silicate, and an exogenous biological material loaded within the YCWP, wherein the YCWP is modified by capping with the silicate, and wherein the biological material comprises a protein or a fragment thereof, nucleic acid, carbohydrate, antigen or a combination thereof, and wherein the biological material is not a tumor lysate, viral antigen, or bacterial antigen.
Orthosilicate-coated yeast cell wall particle composition with non-tumor-lysate exogenous biological material
A composition comprising a yeast cell wall particle (YCWP), a silicate, and an exogenous biological material loaded within the YCWP, wherein the biological material comprises a protein or a fragment thereof, nucleic acid, carbohydrate, or a combination thereof, and wherein the biological material is not a tumor lysate, viral antigen, or bacterial antigen, wherein the YCWP is modified by coating with the silicate, wherein the silicate comprises an organic moiety attached to each of the four oxygen compounds of an orthosilicate.
Across the independent claims, the core claim coverage is directed to compositions that combine silicate-modified YCWPs with loaded exogenous biological material while excluding tumor lysate, viral antigen, and bacterial antigen. The second independent claim further requires orthosilicate structure with an organic moiety attached to each of the four oxygen compounds.
Stated Advantages
Improved retention of the loaded material versus uncapped YCWPs.
Increased delivery or release into cytoplasm after phagocytosis.
Enhanced immunogenic outcomes versus uncapped YCWPs.
Improved survival in an in vivo mouse survival study for silicate-capped tumor-lysate loaded YCWPs, particularly with adjuvants.
Documented Applications
Prophylactic and therapeutic vaccine delivery using silicate-capped YCWP compositions loaded with exogenous biological material.
Delivery to dermal or monocytic/phagocytic cells via phagocytosis.
Cancer treatment by administering the claimed composition to a subject.
Ex vivo incubation of the loaded YCWP with isolated immature dendritic cells prior to administration.
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