Jin-Lei Wang
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
Authors
Professor HANY ELSHEIKHA hany.elsheikha@nottingham.ac.uk
Professor of Interdisciplinary Parasitology
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.
Citation
Wang, J., Elsheikha, H. M., Zhu, W., Chen, K., Li, T., Yue, D., …Zhu, X. (2017). Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice. Frontiers in Immunology, 8, Article 730. https://doi.org/10.3389/fimmu.2017.00730
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, ΔGRA17, 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 |
Contract Date | Jul 3, 2017 |
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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