Synergy of mIL-21 and mIL-15 in enhancing DNA vaccine efficacy against acute and chronic Toxoplasma gondii infection in mice

The synergistic protective efficacy of murine interleukin 21 (mIL-21) and mIL-15 administrated with DNA vaccine against acute and chronic Toxoplasma gondii infection in mice was investigated using T. gondii MIC8 (TgMIC8) as a model. We cloned mIL-21 and mIL-15 from splenic tissues of Kunming mice, and constructed eukaryotic plasmid pVAX/mIL-15, pVAX/mIL-21, and pVAX/mIL-21/mIL-15, respectively. After immunizing with pVAX/TgMIC8 in the presence or absence of these cytokines, immune responses were analyzed using lymphoproliferative assay, cytokine and serum antibody measurements, flow cytometric surface markers on lymphocytes and protection against acute and chronic T. gondii infection. Mice receiving pVAX/TgMIC8 alone developed a strong humoral responses and Th1 type cellular immune responses, and showed an increase of CD4+ and CD8+ T cells compared with all the controls. Adding pVAX/mIL-21 to pVAX/TgMIC8 compared to pVAX/TgMIC8 resulted in only a slight increase in humoral and cellular immune responses, and this immune response was lower than that induced by the pVAX/mIL-15 combined with pVAX/TgMIC8. Co-administration of pVAX/mIL-21/mIL-15 combined with pVAX/TgMIC8 elicited the strongest humoral and cellular immune responses among all the groups, leading to significantly increased survival time against acute infection and the significant reduction of tissue cysts, compared to all the controls. Synergy of mIL-21 and mIL-15 can facilitate specific humoral as well as cellular immune responses elicited by DNA vaccine against acute and chronic T. gondii infection in mice.