title: Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.
abstract: The mounting of a specific immune response against the human papillomavirus type 16 E7 protein (HPV16 E7) is important for eradication of HPV16 E7-expressing cancer cells from the cervical mucosa. To induce a mucosal immune response by oral delivery of the E7 antigen, we expressed the HPV16 E7 antigen on the surface of Lactobacillus casei by employing a novel display system in which the poly-gamma-glutamic acid (gamma-PGA) synthetase complex A (PgsA) from Bacillus subtilis (chungkookjang) was used as an anchoring motif. After surface expression of the HPV16 E7 protein was confirmed by Western blot, flow cytometry and immunofluorescence microscopy, mice were orally inoculated with L. casei-PgsA-E7. E7-specific serum IgG and mucosal IgA productions were enhanced after oral administration and significantly enhanced after boosting. Systemic and local cellular immunities were significantly increased after boosting, as shown by increased counts of lymphocytes (SI = 9.7 +/- 1.8) and IFN-gamma secreting cells [510 +/- 86 spot-forming cells/10(6)cells] among splenocytes and increased IFN-gamma in supernatants of vaginal lymphocytes. Furthermore, in an E7-based mouse tumor model, animals receiving orally administered L. casei-PgsA-E7 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. These results collectively indicate that the oral administration of E7 displayed on lactobacillus induces cellular immunity and antitumor effects in mice.
authors.affiliation: Proteome Research Lab, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea. haryoung@kribb.re.kr
authors.forename: Haryoung
authors.initials: H
authors.lastname: Poo
authors.forename: Hyun-Mi
authors.initials: HM
authors.lastname: Pyo
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Lee
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.forename: Moon-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D007371:Interferon-gamma