CELLULAR VACCINE PLATFORM AND METHODS OF USE

Abstract

Cellular vaccine platforms, such as vaccine immune viral opsonization platforms, for eliciting host immune responses are disclosed. Also disclosed are the methods of making and using the cellular vaccine platforms in stimulating host immune responses.

Description

Claims

1-157. (canceled)

158. A genetically engineered human cell comprising: a. a genomic disruption in at least one human leukocyte antigen (HLA) gene or at least one transcriptional regulator of an HLA gene; andb. an exogenous nucleic acid encoding a cell surface protein that binds to a protein expressed on the surface of a phagocytic or cytolytic immune cell, or a functional fragment or functional variant of said cell surface protein, wherein said binding results in the activation of phagocytic or cytolytic activity of said immune cell, and wherein administration of the genetically engineered human cell to a subject immunizes the subject to an antigen.

159. The genetically engineered human cell of claim 158, wherein said genomic disruption is in an HLA class II gene.

160. The genetically engineered human cell of claim 159, wherein said HLA class II gene is an HLA-DP gene, HLA-DM gene, HLA-DOA gene, HLA-DOB gene, HLA-DQ gene, HLA-DR gene.

161. The genetically engineered human cell of claim 158, wherein said at least one transcriptional regulator of said HLA gene is a CIITA gene, RFX5 gene, RFXAP gene, or RFXANK gene.

162. The genetically engineered human cell of claim 158, wherein said immune cell is an NK cell, a macrophage, a dendritic cell, a neutrophil, or an eosinophil.

163. The genetically engineered human cell of claim 158, wherein said cell surface protein is selected from the group consisting of MICA, MICB, ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, ULBP6, CD155, CD112 (Nectin-2), B7-H6, Necl-2, and immunoglobulin Fc.

164. The genetically engineered human cell of claim 158, further comprising a nucleic acid encoding an exogenous protein, an antigenic fragment thereof, or a suicide gene.

165. The genetically engineered human cell of claim 164, wherein said exogenous protein comprises a microbial protein.

166. A genetically engineered human cell comprising: a. a genomic disruption in at least one human leukocyte antigen (HLA) gene or at least one transcriptional regulator of an HLA gene;b. a nucleic acid encoding an exogenous cell surface protein that binds to a protein expressed on the surface of a phagocytic or cytolytic immune cell, or a functional fragment or functional variant of said exogenous cell surface protein, wherein said binding results in the activation of phagocytic or cytolytic activity of said immune cell; andc. a nucleic acid encoding an exogenous antigenic protein, or an antigenic fragment thereof.

167. The genetically engineered human cell of claim 166, wherein said exogenous antigenic protein, or antigenic fragment thereof, is a microbial protein, or an antigenic fragment thereof.

168. The genetically engineered human cell of claim 167, wherein said microbial protein is secreted by said genetically engineered human cell, expressed on the surface of said genetically engineered human cell, or expressed within the cytoplasm of said genetically engineered human cell.

169. The genetically engineered human cell of claim 167, wherein said microbial protein is a viral, bacterial, parasitic, or protozoa protein.

170. The genetically engineered human cell of claim 169, wherein said microbial protein is a viral protein.

171. The genetically engineered human cell of claim 170, wherein said viral protein is from a virus selected from a group that comprises: influenza, Epstein-Barr virus (EBV), mega virus, Norwalk virus, coxsackie virus, middle east respiratory syndrome-related coronavirus, severe acute respiratory syndrome-related coronavirus, SARS-Cov-2 virus, hepatitis B, varicella zoster virus, parvovirus, adenovirus, Marburg virus, Ebola virus, Rabies, Smallpox, HIV, Hantavirus, Dengue, Rotavirus, MERS-CoV, mumps virus, cytomegalovirus (CMV), Herpes virus, papillomavirus, chikungunya virus, or any combination thereof.

172. A method of immunizing a human subject against a microbe, said method comprising administering to said subject a population of genetically engineered human cells comprising: a. a genomic disruption in at least one MHC gene or at least one transcriptional regulator of an MHC gene, wherein said disruption results in a reduction of activation of T cell proliferation compared to said genetically engineered human cell without said disruption;b. a nucleic acid encoding an exogenous cell surface protein that binds to a protein expressed on the surface of a phagocytic or cytolytic immune cell, or a functional fragment or functional variant of said exogenous cell surface protein, wherein said binding results in the activation of phagocytic or cytolytic activity of said immune cell.

173. The method of claim 172, further comprising a nucleic acid encoding a microbial protein, or an antigenic fragment thereof.

174. The method of claim 172, wherein said administering results in said subject mounting an adaptive immune response against said microbe.

175. The method of claim 172, wherein said administering results in an increase in activation and/or proliferation of T cells that express a T cell receptor that specifically binds said microbial protein or an antigenic fragment thereof.

176. The method of claim 172, wherein said administering results in an increase in activation and/or proliferation of B cells that express a B cell receptor that specifically binds said microbial protein or an antigenic fragment thereof.

177. The method of claim 172, wherein said administering results in an increase in circulating antibodies that specifically bind said microbial protein or antigenic fragment thereof.