title: Analysis of a cholera toxin B subunit (CTB) and human mucin 1 (MUC1) conjugate protein in a MUC1-tolerant mouse model.
abstract: Since epithelial mucin 1 (MUC1) is associated with several adenocarcinomas at the mucosal sites, it is pertinent to test the efficacy of a mucosally targeted vaccine formulation. The B subunit of the Vibrio cholerae cholera toxin (CTB) has great potential to act as a mucosal carrier for subunit vaccines. In the present study we evaluated whether a MUC1 tandem repeat (TR) peptide chemically linked to CTB would break self-antigen tolerance in the transgenic MUC1-tolerant mouse model (MUC1.Tg) through oral or parenteral immunizations. We report that oral immunization with the CTB-MUC1 conjugate along with mucosal adjuvant, unmethylated CpG oligodeoxynucleotide (ODN) and interleukin-12 (IL-12) did not break self-antigen tolerance in MUC1.Tg mice, but induced a strong humoral response in wild-type C57BL/6 mice. However, self-antigen tolerance in the MUC1.Tg mouse model was broken after parenteral immunizations with different doses of the CTB-MUC1 conjugate protein and with the adjuvant CpG ODN co-delivered with CTB-MUC1. Importantly, mice immunized systemically with CpG ODN alone and with CTB-MUC1 exhibited decreased tumor burden when challenged with a mammary gland tumor cell line that expresses human MUC1.
authors.affiliation: Center for Infectious Diseases and Vaccinology (CIDV), The Biodesign Institute at Arizona State University, 1001 South McAllister Avenue, Tempe, AZ 85287-4501, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Pinkhasov
authors.forename: M Lucrecia
authors.initials: ML
authors.lastname: Alvarez
authors.forename: Latha B
authors.initials: LB
authors.lastname: Pathangey
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Tinder
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Mason
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Walmsley
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Gendler
authors.forename: Pinku
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000628:therapy*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology
chemical_list: D001324:Autoantigens; C408982:CPG-oligonucleotide; D018396:Mucin-1; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D002772:Cholera Toxin
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