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

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6903-6911
Number of pages9
JournalVaccine
Volume30
Issue number48
DOIs
Publication statusPublished - Nov 6 2012

Keywords

  • Cancer vaccine
  • Heterologous
  • Listeriolysin-O
  • Prime-boost
  • Treg

ASJC Scopus subject areas

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

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