Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice
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...
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Frontiers Media
2017
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| Online Access: | https://eprints.nottingham.ac.uk/43930/ |
| _version_ | 1848796799156879360 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Wang, Jin-Lei |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:53:43Z |
| format | Article |
| id | nottingham-43930 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:53:43Z |
| publishDate | 2017 |
| publisher | Frontiers Media |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-439302020-05-04T18:52:11Z https://eprints.nottingham.ac.uk/43930/ 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 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. Frontiers Media 2017-06-29 Article PeerReviewed Wang, Jin-Lei, Elsheikha, Hany M., Zhu, Wei-Ning, Chen, Kai, Li, Ting-Ting, Yue, Dong-Mei, Zhang, Xiao-Xuan, Huang, Si-Yang and Zhu, Xing-Quan (2017) Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice. Frontiers in Immunology, 8 . ISSN 1664-3224 Toxoplasma gondii immunization live-attenuated vaccine ΔGRA17 Th1/Th2 cytokines http://journal.frontiersin.org/article/10.3389/fimmu.2017.00730/full doi:10.3389/fimmu.2017.00730 doi:10.3389/fimmu.2017.00730 |
| spellingShingle | Toxoplasma gondii immunization live-attenuated vaccine ΔGRA17 Th1/Th2 cytokines 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 |
| title | Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice |
| title_full | Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice |
| title_fullStr | Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice |
| title_full_unstemmed | Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice |
| title_short | Immunization with Toxoplasma gondii GRA17 deletion mutant induces partial protection and survival in challenged mice |
| title_sort | immunization with toxoplasma gondii gra17 deletion mutant induces partial protection and survival in challenged mice |
| topic | Toxoplasma gondii immunization live-attenuated vaccine ΔGRA17 Th1/Th2 cytokines |
| url | https://eprints.nottingham.ac.uk/43930/ https://eprints.nottingham.ac.uk/43930/ https://eprints.nottingham.ac.uk/43930/ |