Oral administration of human papillomavirus type 16 E7 displayed on Lactobacillus casei induces E7-specific antitumor effects in C57/BL6 mice.
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.
Poo
Haryoung
H
Proteome Research Lab, Korea Research Institute of Bioscience and Biotechnology, Daejon, Korea. haryoung@kribb.re.kr
Pyo
Hyun-Mi
HM
Lee
Tae-Young
TY
Yoon
Sun-Woo
SW
Lee
Jong-Soo
JS
Kim
Chul-Joong
CJ
Sung
Moon-Hee
MH
Lee
Seung-Hoon
SH
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
D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D007371:Interferon-gamma