VACCINE DELIVERY SYSTEMS USING YEAST CELL WALL PARTICLES
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.
1 . A composition for delivering a vaccine, comprising (i) a particle; and (ii) an exogenous biological material loaded within the particle, wherein the biological material comprises a protein or a fragment thereof, nucleic acid, carbohydrate, tumor lysate, or a combination thereof.
2 . The composition of claim 1 , wherein the particle is a yeast cell wall particle.
3 . The composition of claim 1 , wherein the biological material is tumor lysate.
4 . The composition of claim 3 , wherein the tumor lysate is obtained from tumor cell lines.
5 . The composition of claim 2 , further comprises a silicate, wherein the yeast cell wall particle is modified by capping with the silicate.
6 . The composition of claim 5 , wherein the silicate comprises an organic moiety attached to each of the four oxygen compounds of an orthosilicate.
7 . The composition of claim 5 , wherein the silicate is selected from the group consisting of tetraethylorthosilicate, tetramethylorthosilicate, tetrapropylorthosilicate, and tetrabutylorthosilicate.
8 . The composition of claim 1 , wherein the biological material loaded particle is further incubated with an isolated dendritic cell prior to administration.
9 . The composition of claim 1 , further comprises one or more adjuvants, excipients, and preservatives.
10 . The composition of claim 9 , wherein the adjuvant is monophosphoryl lipid A or a CpG oligonucleotide.
11 . A method for producing an incubated dendritic cell containing a vaccine loaded particle, comprising:
(i) loading a biological material into the particle to produce a biological material loaded particle;
(ii) freeze-drying the biological material loaded particle; and
(iii) incubating the biological material loaded particle with a dendritic cell, wherein the biological material comprises a protein or a fragment thereof, nucleic acid, carbohydrate, tumor lysate, or a combination thereof; and
wherein incubating the biological material loaded particle with the dendritic cell causes the dendritic cell to phagocytose the biological material loaded particle.
12 . The method of claim 11 , further comprising (a) resuspending the biological material loaded particle in solution and (b) freeze-drying the resuspended solution before step (iii).
13 . The method of claim 11 , wherein step (iii) comprises: (a) contacting the biological material loaded particle with the dendritic cell at a ratio of from about 1:1 to about 100:1, (b) incubating the biological material loaded particle with the dendritic cell; and (c) collecting the dendritic cell containing the loaded particle and washing the cell.
14 . A method for treating an infectious disease, comprising administering the composition of claim 1 to a subject.
15 . A method for treating cancer, comprising administering the composition of claim 1 to a subject.
16 . The method of claim 12 , wherein the cancer is selected from the group consisting of breast cancer, small cell lung cancer, non-small cell lung cancer, glioma, medulloblastoma, neuroblastoma, Wilms tumors, rhabdomyosarcoma, osteosarcoma, liver cancer, pancreatic cancer, melanoma, prostate cancer and ocular melanoma.
17 . A method for preparing a composition comprising a yeast cell wall particle and a silicate, comprising contacting the yeast cell wall particle with the silicate in the presence of ammonia such that the yeast cell wall particle is capped by the silicate.
18 . A method for producing a cell mixture containing a yeast cell wall particle loaded with a biological material and capped with a silicate, comprising:
(i) loading a biological material into a yeast cell wall particle to produce a loaded particle;
(ii) capping the loaded particle with a silicate;
(iii) freeze-drying the capped, loaded particle; and
(iv) incubating the capped, loaded particle with a cell of monocytic origin
wherein the incubation causes the cell of monocytic origin to phagocytose the capped, loaded particle.
19 . The method of claim 18 , wherein step (i) comprises:
(a) suspending a yeast cell wall particle and a biological material in a diluent and incubating for a period of time to allow the biological material to be absorbed by the yeast cell wall particle; and
(b) freeze-drying the suspension to load the biological material within the yeast cell wall particle.
20 . The method of claim 18 , wherein steps (a) and (b) are repeated at least once.