Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in heterologous prime-boost vaccination against cancer

Ming Shen Dai, Georges Vassaux, Man Xu, Ren In You, Yu Feng Hsieh, Laure Hélène Ouisse, Kai Yu Lo, Huey Kang Sytwu, Tsu Yi Chao

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6 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)6903-6911
頁數9
期刊Vaccine
30
發行號48
DOIs
出版狀態已發佈 - 十一月 6 2012

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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