AbstractThe inhibitor of apoptosis protein survivin is highly expressed in neuroblastoma (NB) and survivin‐specific T cells were identified in Stage 4 patients. Therefore, we generated a novel survivin minigene DNA vaccine (pUS‐high) encoding exclusively for survivin‐derived peptides with superior MHC class I (H2‐Kk) binding affinities and tested its efficacy to suppress tumor growth and metastases in a syngeneic NB mouse model. Vaccination was performed by oral gavage of attenuated Salmonella typhimurium SL7207 carrying pUS‐high. Mice receiving the pUS‐high in the prophylactic setting presented a 48–52% reduction in s.c. tumor volume, weight and liver metastasis level in contrast to empty vector controls. This response was as effective as a survivin full‐length vaccine and was associated with an increased target cell lysis, increased presence of CD8+ T‐cells at the primary tumor site and enhanced production of proinflammatory cytokines by systemic CD8+ T cells. Furthermore, depletion of CD8+ but not CD4+ T‐cells completely abrogated the pUS‐high mediated primary tumor growth suppression, demonstrating a CD8+ T‐cell mediated effect. Therapeutic vaccination with pUS‐high led to complete NB eradication in over 50% of immunized mice and surviving mice showed an over 80% reduction in primary tumor growth upon rechallenge in contrast to controls. In summary, survivin‐based DNA vaccination is effective against NB and the rational minigene design provides a promising approach to circumvent potentially hazardous effects of using full length antiapoptotic genes as DNA vaccines. © 2009 UICC