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Abstract Background Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut. Blocking IL-10 at the time of immunization may result in unwanted side effects, especially immune-pathological diseases in the intestine. Methods We investigated whether blocking IL-10 at the time of immunization results in intestinal inflammation responses in a mouse TC-1 tumour model and in a NOD autoimmune disease prone mouse model. Results We now show that blocking IL-10 at the time of immunization increases IL-10 production by CD4+ T cells in the spleen and draining lymph nodes, and does not result in blood cell infiltration to the intestines leading to intestinal pathological changes. Moreover, immunization with papillomavirus like particles combined with simultaneously blocking IL-10 signalling does not increase the incidence of autoimmune disease in Non-obese diabetic (NOD) mice. Conclusions Our results indicate that immunization with an IL-10 inhibitor may facilitate the generation of safe, effective therapeutic vaccines against chronic viral infection and cancer.