Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice
Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute, Chronic, and Congenital Toxoplasmosis in Mice
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DOI：
10.4049/jimmunol.1900410
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发表时间：
2020-01
期刊：
影响因子：
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通讯作者：
Jin-Lei Wang;Qin-Li Liang;Ting-Ting Li-Ting;Jun-Jun He-Jun;M. Bai;Xue-Zhen Cao;H. Elsheikha;Xing-Quan Zhu
中科院分区：
文献类型：
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作者：
Jin-Lei Wang;Qin-Li Liang;Ting-Ting Li-Ting;Jun-Jun He-Jun;M. Bai;Xue-Zhen Cao;H. Elsheikha;Xing-Quan Zhu
Key Points Vaccination with RHΔtkl1 in mice induces a strong humoral and cellular response. RHΔtkl1-vaccinated mice are protected against acute, chronic, and congenital toxoplasmosis. Immunity induced by RHΔtkl1 vaccine is primarily Th1 biased and CD8+ T cell mediated. In this study, we generated a tkl1 deletion mutant in the Toxoplasma gondii type 1 RH (RHΔtkl1) strain and tested the protective efficacies of vaccination using RHΔtkl1 tachyzoites against acute, chronic, and congenital T. gondii infections in Kunming mice. Mice vaccinated with RHΔtkl1 mounted a strong humoral and cellular response as shown by elevated levels of anti–T. gondii–specific IgG, IL-2, IL-12, IFN-γ, and IL-10. All RHΔtkl1-vaccinated mice survived a lethal challenge with 1 × 103 tachyzoites of type 1 RH or ToxoDB#9 (PYS or TgC7) strain as well as 100 cysts or oocysts of Prugniuad strain. All mock-vaccinated plus infected mice have died. Vaccination also protected against cyst- or oocyst-caused chronic infection, reduced vertical transmission caused by oocysts, increased litter size, and maintained body weight of pups born to dams challenged with 10 oocysts on day 5 of gestation. In contrast, all mock-vaccinated plus oocysts-infected dams had aborted, and no fetus has survived. Vaccinated dams remained healthy postinfection, and their brain cyst burden was significantly reduced compared with mock-vaccinated dams infected with oocysts. In vivo depletion of CD4+ T cells, CD8+ T cells, and B cells revealed that CD8+ T cells are involved in the protection of mice against T. gondii infection. Additionally, adoptive transfer of CD8+ T cells from RHΔtkl1-vaccinated mice significantly enhanced the survival of naive mice infected with the pathogenic strain. Together, these data reaffirm the importance of CD8+ T cell responses in future vaccine design for toxoplasmosis and present T. gondii tkl1 gene as a promising vaccine candidate.
