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Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice

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

Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice Thumbnail


Authors

Jin-Lei Wang

Wei-Ning Zhu

Kai Chen

Ting-Ting Li

Dong-Mei Yue

Xiao-Xuan Zhang

Si-Yang Huang

Xing-Quan Zhu



Abstract

Toxoplasmosis remains a world-threatening disease largely because of the lack of a fully effective vaccine. Here, we created a ΔGRA17 mutant by disrupting the virulence factor GRA17 using CRISPR-Cas9 method. Then, we tested whether ΔGRA17 tachyzoites can be used as a live-attenuated vaccine against acute, chronic, and congenital Toxoplasma gondii infection in mice. Immune response evoked by ΔGRA17 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. ΔGRA17-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 ΔGRA17-immunized dams were not different compared to pups born to naïve 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 ΔGRA17 strain evokes cell-mediated and neutralizing antibody responses and confers some degree of protection against challenge with homologous and heterologous virulent T. gondii strains.

Journal Article Type Article
Acceptance Date Jun 9, 2017
Online Publication Date Jun 29, 2017
Publication Date Jun 29, 2017
Deposit Date Jul 3, 2017
Publicly Available Date Jul 3, 2017
Journal Frontiers in Immunology
Electronic ISSN 1664-3224
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 8
Article Number 730
DOI https://doi.org/10.3389/fimmu.2017.00730
Keywords Toxoplasma gondii, immunization, live-attenuated vaccine, ?GRA17, Th1/Th2 cytokines
Public URL https://nottingham-repository.worktribe.com/output/868821
Publisher URL http://journal.frontiersin.org/article/10.3389/fimmu.2017.00730/full

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