title: Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in heterologous prime-boost vaccination against cancer.
abstract: Studies have shown that an enhanced CD8+ T cell response and better tumor protection can be achieved by heterologous prime-boost vaccination in mice. Such heterologous vaccination can be more immunogenic than the homologous setting. We previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell (Treg)-directed suppression. In the present study, we assessed the combination of this approach with plasmid DNA vaccination, in a prime-boost immunization strategy. E. coli-LLO bacteria expressing ovalbumin (OVA) and plasmid pcDNA-encoding OVA were used to vaccinate naive or B16-OVA tumor-bearing C57B6 mice. The anticancer activity was measured in a tumor prevention or therapeutic model. Higher OVA-specific CD8+ T cell responses and greater tumor inhibition were seen in the bacterial-prime/plasmid-boost setting than with the homologous and reversed sequences. This tumor protection effect from heterologous prime-boost remained in the therapeutic model. When examining the Treg effect during the prime-boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. Our studies offer the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced antitumor effect in conjunction with DNA in a heterologous prime-boost protocol, and suggest that early Treg inhibition is crucial to a successful immunization against cancer.
authors.affiliation: Division of Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Centre, Taipei, Taiwan.
authors.forename: Ming-Shen
authors.initials: MS
authors.lastname: Dai
authors.forename: Georges
authors.initials: G
authors.lastname: Vassaux
authors.forename: Man
authors.initials: M
authors.lastname: Xu
authors.forename: Ren-In
authors.initials: RI
authors.lastname: You
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Hsieh
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Ouisse
authors.forename: Kai-Yu
authors.initials: KY
authors.lastname: Lo
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Chao
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006460:Hemolysin Proteins / Q000096:biosynthesis*; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000517:prevention & control / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D019496:Cancer Vaccines; D022361:Escherichia coli Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D019444:Vaccines, DNA; C038705:hlyA protein, Listeria monocytogenes