[Background] Earlier studies have shown that higher CD8+ T-cell response and better tumor protection can be achieved by heterologous prime-boost vaccination in mice. We previously demonstrated that a Listeriolysin-O (LLO)-expressing E. coli vaccine can enhanced CD8-cytotoxic T cell (CTL) responses by mitigating regulatory T cells (Treg)-mediated suppression. We herein employed this Treg-inhibiting vaccine into the prime/boost immunization strategy. [Methods] Bacteria E. coli-LLO expressing Ovalbumin (OVA) and plasmid pcDNA—encoding OVA were used as specific antigen immunization. C57B6 mice and syngenic melanoma cell line B16-OVA were used in tumor challenge model. CD25 monoclonal antibody (PC-61) was used for Treg depletion. [Results] Higher OVA-specific CD8+ T-cell responses and superior tumor inhibition were seen in the bacterial-prime/plasmid-boost setting than homologous or reversed sequence. This tumor protection effect from heterologous prime/boost remained significant 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. [Conclusion] Our studies offer the first evidence that a Listeriolysin-O E. coli vaccine can induce superior anti-tumor effect in conjunction with DNA in a heterologous prime-boost protocol and proposed that early Treg inhibition is crucial to a successful immunization against cancer.
Date:
2011-04
Relation:
Journal of Immunology. 2011 Apr;186(Suppl. 1):Meeting Abstract 165.49.
