title: Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.
abstract: Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Shailbala
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Guojun
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America; Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Schluns
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America; Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Anthony
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America; Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States of America.
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000286:Administration, Sublingual; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage; D056724:Immunity, Humoral; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D008810:Mice, Inbred C57BL; D009061:Mouth Mucosa / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D010047:Ovalbumin