Immunization with Toxoplasma gondii GRA17 Deletion Mutant Induces Partial Protection and Survival in Challenged Mice

文献类型： 外文期刊

第一作者： Wang, Jin-Lei

作者： Wang, Jin-Lei;Zhu, Wei-Ning;Chen, Kai;Li, Ting-Ting;Yue, Dong-Mei;Zhang, Xiao-Xuan;Huang, Si-Yang;Zhu, Xing-Quan;Elsheikha, Hany M.;Zhu, Wei-Ning

作者机构：

关键词： Toxoplasma gondii;immunization;live-attenuated vaccine;Delta GRA17;Th1/Th2 cytokines

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：7.561； 五年影响因子：7.624 ）

ISSN： 1664-3224

年卷期： 2017 年 8 卷

页码：

收录情况： SCI

摘要： Toxoplasmosis remains a world-threatening disease largely because of the lack of a fully effective vaccine. Here, we created a Delta GRA17 mutant by disrupting the virulence factor GRA17 using CRISPR-Cas9 method. Then, we tested whether Delta GRA17 tachyzoites can be used as a live-attenuated vaccine against acute, chronic, and congenital Toxoplasma gondii infection in mice. Immune response evoked by Delta GRA17 immunization suggested a sequential Th1 and Th2 T cell response, indicated by high levels of Th1 and a mixed Th1/Th2 cytokines at 28 and 70 days after immunization, respectively. Delta GRA17-mediated immunity fully protected mice against lethal infection with wild-type (wt) RH strain, heterologous challenge with PYS, and TgC7 strains of the Chinese ToxoDB#9 genotype, and T. gondii Pru strain. Although parasite cysts were detected in 8 out of 10 immunized mice, cyst burden in the brain was significantly reduced (P < 0.05) in immunized mice (53 +/- 15 cysts/brain) compared to non-immunized mice (4,296 +/- 687 cysts/brain). In respect to congenital infection, the litter size, survival rate, and body weight (BW) of pups born to Delta GRA17-immunized dams were not different compared to pups born to naive control dams (P = 0.24). However, a marked reduction in the litter size (P < 0.001), survival rate, and BW (P < 0.01) of pups born to non-immunized and infected dams was detected. Also, immunized dams infected with type II Pru strain had significantly (P < 0.001) less cyst burden in the brain compared with non-immunized and infected dams. These findings show that immunization with Delta GRA17 strain evokes cell-mediated and neutralizing antibody responses and confers some degree of protection against challenge with homologous and heterologous virulent T. gondii strains.

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